The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)
Tumors or cancer of the human BREAST.
Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.
Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.
An individual having different alleles at one or more loci regarding a specific character.
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Any neoplasms of the male breast. These occur infrequently in males in developed countries, the incidence being about 1% of that in females.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Biochemical identification of mutational changes in a nucleotide sequence.
The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Excision of one or both of the FALLOPIAN TUBES.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An exchange of DNA between matching or similar sequences.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
A cell line derived from cultured tumor cells.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
Benign or malignant neoplasms of the FALLOPIAN TUBES. They are uncommon. If they develop, they may be located in the wall or within the lumen as a growth attached to the wall by a stalk.
Established cell cultures that have the potential to propagate indefinitely.
Identification of genetic carriers for a given trait.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.
Transport proteins that carry specific substances in the blood or across cell membranes.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Deletion of sequences of nucleic acids from the genetic material of an individual.
DNA present in neoplastic tissue.
A family of RNA-binding proteins that are homologues of ELAV protein, Drosophila. They were initially identified in humans as the targets of autoantibodies in patients with PARANEOPLASTIC ENCEPHALOMYELITIS. They are thought to regulate GENE EXPRESSION at the post-transcriptional level.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
"Novel consensus DNA-binding sequence for BRCA1 protein complexes". Molecular Carcinogenesis. 38 (2): 85-96. doi:10.1002/mc. ... "Members of the USF family of helix-loop-helix proteins bind DNA as homo- as well as heterodimers". Gene Expression. 2 (3): 231- ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi: ... Upstream stimulatory factor 2 is a protein that in humans is encoded by the USF2 gene. This gene encodes a member of the basic ...
Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene. The protein encoded by this gene is ... "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. ... It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. This ... "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. ...
This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds ... Cofactor of BRCA1, TH1L, and WHSC2. ENSG00000206357, ENSG00000231044, ENSG00000204356, ENSG00000206268, ENSG00000233801 GRCh38 ... "The human RD protein is closely related to nuclear RNA-binding proteins and has been highly conserved". Gene. 90 (2): 299-302. ... "Entrez Gene: RDBP RD RNA binding protein". Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, ...
Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved ... Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (May 2001). "Direct DNA binding by Brca1". Proceedings of the National ... Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved ... Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (May 2001). "Direct DNA binding by Brca1". Proceedings of the National ...
It binds to the DNA sequence 5'-TGA[CG]TCA-3'. JUNB has been shown to interact with BRCA1, and SMAD3. AP-1 (transcription ... "Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions". Mol. Cell. Biol. 17 (6): 3094-102 ... JUNB+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... Liberati NT, Datto MB, Frederick JP, Shen X, Wong C, Rougier-Chapman EM, Wang XF (Apr 1999). "Smads bind directly to the Jun ...
Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. CSTF2 has been shown to interact ... Kleiman, F E; Manley J L (September 1999). "Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF- ... This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage ... 2001). "The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene ...
Auriol E, Billard LM, Magdinier F, Dante R (2005). "Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 ... Commercial testing for BRCA1 and BRCA2 gene mutations has been available in most developed countries since at least 2004. In ... Hereditary non-BRCA1 and non-BRCA2 breast tumors (and even some sporadic carcinomas) are believed to result from the expression ... If a mother or a sister was diagnosed breast cancer, the risk of a hereditary BRCA1 or BRCA2 gene mutation is about 2-fold ...
The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The ... 2004). "A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway ... protein localizes to the nucleoplasm and nucleoli, and interacts with p53, retinoblastoma-1 and BRCA1. It modulates p53 ... IFI16+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ...
In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. BRG1 works to ... The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi: ... The encoded protein is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for ...
Fanconi anemia group J protein is a protein that in humans is encoded by the BRCA1-interacting protein 1 (BRIP1) gene. The ... BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This ... "Entrez Gene: BRIP1 BRCA1 interacting protein C-terminal helicase 1". Rafnar T, Gudbjartsson DF, Sulem P, Jonasdottir A, ... Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM (February 2004). "The BRCA1-associated protein BACH1 is a ...
"Defining biochemical functions for the BRCA1 tumor suppressor protein: analysis of the BRCA1 binding protein BAP1". Cancer ... Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, Fukuda M, Ohta T (Jan 2009). "BRCA1-associated protein 1 interferes with BRCA1/ ... a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression". Oncogene ... BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) is a deubiquitinating enzyme that in humans is encoded by the ...
Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by ... "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... "Entrez Gene: TP53BP1 tumor protein p53 binding protein 1". Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der ... Choubey D, Lengyel P (Mar 1995). "Binding of an interferon-inducible protein (p202) to the retinoblastoma protein". The Journal ...
... plays a role in regulating calcium-dependent transcription and interacts with cAMP-response-element-binding protein (CREB ... This locus also interacts with high-penetrance mutations BRCA1 and BRCA2 to increase risk. The rs3803662 variant has a high ... and CREB-binding protein (CBP). It also increases transcription via interaction with CITED1, a transcription co-regulator that ... The protein TOX3 has a glutamine-rich C-terminus due to CAG repeats. TOX3 is located on human chromosome band 16q12.1. The gene ...
BRCA1/2 are genes that produce proteins which regulate the DNA repair pathway by binding to Rad51. Loss of heterozygosity can ... The genes BRCA1 and BRCA2 show loss of heterozygosity in samplings of tumors from patients who have germline mutations. ... "Mapping loss of heterozygosity in normal human breast cells from BRCA1/2 carriers" - BJC "Loss of Heterozygosity Studies on ...
... which will bind to the major and/or minor binding sites on importin-α. Once the cargo protein is bound, importin-β interacts ... In addition, importin-α has been shown to transport the tumour suppressor gene, BRCA1 (breast cancer type 1 susceptibility ... which facilitates binding to the NLS of specific cargo proteins. The major NLS binding site is found towards the N-terminus, ... but the key proteins involved had not been elucidated up until that point. A 60 kDa cytosolic protein, essential for protein ...
The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other ... BRCA1 associated protein is a protein that in humans is encoded by the BRAP gene. ... "Entrez Gene: BRCA1 associated protein". Retrieved 2018-03-23. Matheny SA, Chen C, Kortum RL, Razidlo GL, Lewis RE, White MA ( ... It is a cytoplasmic protein which may regulate nuclear targeting by retaining proteins with a nuclear localization signal in ...
... which appears to act as a phospho-protein binding domain. Human proteins containing this domain include: BARD1; BRCA1 CTDP1; ... BRCA1 C Terminus (BRCT) domain is a family of evolutionarily related proteins. It is named after the C-terminal domain of BRCA1 ... Yu X, Chini CC, He M, Mer G, Chen J (2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639-642 ... Eukaryotic Linear Motif resource motif class LIG_BRCT_BRCA1_1 Eukaryotic Linear Motif resource motif class LIG_BRCT_BRCA1_2 ...
... is essential for binding to DDB1 (a larger 127 kDa protein). Together, the two proteins form a UV-damaged DNA binding protein ... El-Deiry WS (2003). "Transactivation of repair genes by BRCA1". Cancer Biology & Therapy. 1 (5): 490-1. doi:10.4161/cbt.1.5.162 ... DNA damage-binding protein 2 is a protein that in humans is encoded by the DDB2 gene. As indicated by Rapić-Otrin et al. in ... Zhu Q, Battu A, Ray A, Wani G, Qian J, He J, Wang QE, Wani AA (June 2015). "Damaged DNA-binding protein down-regulates ...
CtIP binds to the BRCT repeats within the breast cancer gene BRCA1 and enables CtBP to influence BRCA1 activity. Both proteins ... That is, regulatory proteins that bind to sequence-specific DNA-binding proteins and help turn genes off. CtBPs do this by ... C-terminal-binding protein interacting protein (CtIP) is a binding partner with CtBP, which contribute to transcription ... "Entrez Gene: CTBP1 C-terminal binding protein 1". Bruton RK, Rasti M, Mapp KL, Grand R (2007). "C-terminal-binding protein ...
"Entrez Gene: ETV4 Ets variant gene 4 (E1A enhancer binding protein, E1AF)". "ETV4 Gene - GeneCards , ETV4 Protein , ETV4 ... "The search for BRCA1". Cancer Research. 54 (24): 6374-82. PMID 7987831. Higashino F, Yoshida K, Fujinaga Y, Kamio K, Fujinaga K ... Feb 1993). "Isolation of a cDNA encoding the adenovirus E1A enhancer binding protein: a new human member of the ets oncogene ... encoding the adenovirus E1A enhancer-binding protein, in extraosseous Ewing's sarcoma". Biochemical and Biophysical Research ...
protein binding. • transferase activity. Cellular component. • cytoplasm. • BRCA1-A complex. • BRCA1-BARD1 complex. • ubiquitin ... metal ion binding. • protein homodimerization activity. • kinase binding. • RNA binding. • protein heterodimerization activity ... BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.[5][6][7] The human BARD1 ... Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, Fukuda M, Ohta T (Jan 2009). "BRCA1-associated protein 1 interferes with BRCA1/ ...
Takahashi I, Kameoka Y, Hashimoto K (Aug 2002). "MacroH2A1.2 binds the nuclear protein Spop". Biochimica et Biophysica Acta ( ... "BRCA1 supports XIST RNA concentration on the inactive X chromosome". Cell. 111 (3): 393-405. doi:10.1016/S0092-8674(02)01052-8 ... Core histone macro-H2A.1 is a protein that in humans is encoded by the H2AFY gene. Histones are basic nuclear proteins that are ... "Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones ...
BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The ... BRCA2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate and maintain strand invasion, ... Although the structures of the BRCA1 and BRCA2 genes are very different, at least some functions are interrelated. The proteins ... also called by the synonym breast cancer type 2 susceptibility protein, is responsible for repairing DNA. BRCA2 and BRCA1 are ...
This protein, heterochromatin protein 1 (HP1)-beta (CBX1), is bound to histone H3 methylated on lysine 9 (H3K9me). Half-maximum ... This allows the recruitment of BRCA1 and 53BP1 to the long, modified γH2AX/MDC1 chromatin. Other proteins that stably assemble ... Ward IM, Minn K, Jorda KG, Chen J (May 2003). "Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to ... MDC1 (mediator of DNA damage checkpoint protein 1) then binds to γH2AX and the γH2AX/MDC1 complex then orchestrates further ...
Baldassarre et al., showed that HMGA1 protein binds to the promoter region of DNA repair gene BRCA1 and inhibits BRCA1 promoter ... "Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast ... RAP80, a subunit of the DNA repair breast cancer type 1 susceptibility protein complex (BRCA1-A), binds ubiquitin attached to ... These proteins have three highly positively charged regions, termed AT hooks, that bind the minor groove of AT-rich DNA ...
Kim H, Chen J, Yu X (2007). "Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response". Science. 316 (5828 ... BRCA1-A complex subunit RAP80 is a protein that in humans is encoded by the UIMC1 gene. GRCh38: Ensembl release 89: ... 2007). "Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response". Science. 316 (5828): 1194-8. doi: ... 2007). "The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair ...
Histone-binding protein RBBP7 is a protein that in humans is encoded by the RBBP7 gene. This protein is a ubiquitously ... It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor ... Zhang Q, Vo N, Goodman RH (2000). "Histone binding protein RbAp48 interacts with a complex of CREB binding protein and ... It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The ...
Yamane K, Chen J, Kinsella TJ (Jun 2003). "Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle ... DNA topoisomerase 2-binding protein 1 is an enzyme that in humans is encoded by the TOPBP1 gene. This gene encodes a binding ... Nakayama M, Kikuno R, Ohara O (Nov 2002). "Protein-protein interactions between large proteins: two-hybrid screening using a ... Yu X, Chini CC, He M, Mer G, Chen J (Oct 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639 ...
LIM domain-binding protein 1 is a protein that in humans is encoded by the LDB1 gene. LDB1 has been shown to interact with LMO4 ... 2002). "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity ... 2002). "Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to regulate development". Proc. Natl. Acad. Sci. U.S.A ... "Ssdp proteins bind to LIM-interacting co-factors and regulate the activity of LIM-homeodomain protein complexes in vivo". ...
... a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase ... Joukov V, Groen AC, Prokhorova T, Gerson R, White E, Rodriguez A, Walter JC, Livingston DM (Nov 2006). "The BRCA1/BARD1 ... RHAMM also binds directly with ERK1 and forms complexes with ERK1,2 and MEK1, suggesting a role as a scaffold protein that ... Turley EA, Austen L, Vandeligt K, Clary C (Mar 1991). "Hyaluronan and a cell-associated hyaluronan binding protein regulate the ...
BRCA1 is posttranscriptionally regulated by RNA-binding proteins, the identities of which are unknown. HuR is an RNA binding ... Posttranscriptional regulation of the breast cancer susceptibility gene BRCA1 by the RNA binding protein HuR. Saunus, J., ... Posttranscriptional regulation of the breast cancer susceptibility gene BRCA1 by the RNA binding protein HuR ... Posttranscriptional regulation of the breast cancer susceptibility gene BRCA1 by the RNA binding protein HuR ...
... a BRCA1 promoter-regulated luciferase construct indicated that the CtBP2 complex binds the BRCA1 promoter and represses BRCA1 ... We have recently demonstrated that the transcriptional co-repressor C-terminal binding protein 2 (CtBP2) is overexpressed in ... We have recently demonstrated that the transcriptional co-repressor C-terminal binding protein 2 (CtBP2) is overexpressed in ... Conclusion CtBP2 is an ovarian cancer oncogene that may play a significant role in epigenetically silencing BRCA1 function in ...
... for protein-protein interaction assays and cell growth assays. ... Recombinant BRCA1 is suitable for in vitro studies of ... for Recombinant BRCA1 proteinProtein Details. The wild-type BRCA1 protein (1-1863 residues, accession number NM_007294) was ... for Recombinant BRCA1 proteinContents. 2 µg of Recombinant BRCA1 protein and Dilution Buffer AM1 (20 mM Tris-Cl (pH 8), 20% ... for Recombinant BRCA1 proteinBackground. Breast cancer type 1 susceptibility (BRCA1) protein is a tumor suppressor that is ...
... but the biological function of the BRCA1 protein has remained largely elusive. The recent correspondence of Koonin et al. [ ... Inherited mutations in BRCA1 predispose to breast and ovarian cancer, ... as this domain shows similarities with the C-terminal regions of a p53-binding protein (53BP1), the yeast RAD9 protein involved ... Inherited mutations in BRCA1 predispose to breast and ovarian cancer, but the biological function of the BRCA1 protein has ...
Cyclic AMP Response Element-Binding Protein / chemistry * DNA / metabolism * DNA Methylation* * Deoxyribonuclease I / ... Functional analysis of CpG methylation in the BRCA1 promoter region Oncogene. 2001 Aug 30;20(38):5331-40. doi: 10.1038/sj.onc. ... Gel mobility shift and competition assays identified a DNA-protein complex recognizing the CRE motif that we were able to ... Our objectives were to characterize the functional effects of DNA methylation in the BRCA1 promoter and to clarify the ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds Lys-63-linked ubiquitin (PubMed:19328070, Ref. ... Plays a central role in the BRCA1-A complex by specifically binding Lys-63-linked ubiquitinated histones H2A and H2AX at DNA ... at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, ...
The key function of the FA pathway is to orchestrate proteins involved in the repair of interstrand cross-links (ICLs), to ... BRCA1-interacting protein helicase. Promotes HR through BRCA1 binding. DNA-dependent ATPase activity. Ovarian cancer ... 5. FA Proteins and Cancer Predisposition. The identification of the relevant role of BRCA1 and BRCA2 tumor suppressor genes [ ... The AAA+ protein ATAD3 has displacement loop binding properties and is involved in mitochondrial nucleoid organization. J. Cell ...
In combination with the AP-1/CRE sites, the Sp-binding domain enhanced the recruitment of nuclear proteins to the BRCA1 ... and downstream by a half CRE-binding motif (5-CGTAA-3) that binds CRE-binding protein. In ER-α-positive MCF-7 cells and ER-α- ... comprises cis-acting elements that are targeted by Sp-binding and CRE-binding proteins that contribute to regulation of BRCA1 ... 1 or specificity protein (Sp)-binding sites. Interestingly, the BRCA1 gene lacks a consensus estrogen response element. We ...
ubiquitin-protein transferase activity Source: InterPro. *zinc ion binding Source: InterPro. View the complete GO annotation on ... View protein in InterPro. IPR011364. BRCA1. IPR031099. BRCA1-associated. IPR025994. BRCA1_serine_dom. ... View protein in InterPro. IPR011364. BRCA1. IPR031099. BRCA1-associated. IPR025994. BRCA1_serine_dom. ... Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. Q9JKL6. A0A0F7PZU8. M9P100. A0A0F7PX11. V9XUB5. ...
Here we report the investigation of a hyper-IgD syndrome caused by deficiency of the DNA damage-response protein p53-binding ... BRCA1 C terminus. The phosphoinositide 3-kinase-like kinase (PIKK) S/TQ phosphorylation sites are labeled (Ser6, Ser25, Ser29, ... Arrows indicate primer binding sites for PCR reactions. The probe binding site is highlighted in red. ... A) Binding of serum IgD, IgM, and IgA to intestinal bacteria. Serum from 12- to 14-wk-old Trp53bp1−/−, Ighm−/−, Trp53bp1−/−; ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... The BRCT domain is a phospho-protein binding domain.. Science 302 639-42 2003 ... The aimal BRCA1 protein is a E3 ubiquitin-protein ligase that specifically mediates the formation of Lys-6-linked ...
androgen receptor binding. • RNA binding. • ubiquitin protein ligase binding. • transcription regulatory region DNA binding. • ... tubulin binding. • metal ion binding. • enzyme binding. • zinc ion binding. • damaged DNA binding. • ligação a proteínas ... RNA polymerase binding. • identical protein binding. Componente celular. • BRCA1-BARD1 complex. • condensed nuclear chromosome ... Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding». ...
Defining biochemical functions for the BRCA1 tumor suppressor protein: analysis of the BRCA1 binding protein BAP1. Cancer Lett ... Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle checkpoint. Cancer Res 2003; 63: 3049-53. ... BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. ... HCC1937-BRCA1). It is prudent to note that although HCC1937 cells lack WT BRCA1, they express a truncated form of the protein ...
In vitro Analysis of Binding to a COOH-Terminal Fragment of BRCA1. GST/BRCA1-1293-1863 and MBP/PALB2-1-70 fusion proteins in 50 ... PALB2 Directly Binds BRCA1 and Functionally Links BRCA1 to BRCA2. Given that PALB2 independently interacts with BRCA1 and BRCA2 ... results suggest that PALB2 directly binds to BRCA1 and may physically link BRCA2 to BRCA1 by independently binding each protein ... were incubated with GST or GST/BRCA1-1293-1863 beads. Binding of each MBP fusion protein to GST or GST/BRCA1-1293-1863 was ...
B) In vitro interaction assay using recombinant GST-BRCA1 fragments performed in HeLa cells. GSH bead-bound proteins were ... there are specific insertion/deletion mutations located close to R-loop-mediated BRCA1 binding sites within TRs. Thus, BRCA1/ ... BRCA1 Binds the Transcription Termination Region of a Substantial Subset of Actively Expressed Mammalian Genes. (A) Diagram of ... C) Gene expression comparison between genes with (red) and without (blue) BRCA1 bound to relevant TR. Boxplots reflect the ...
... we briefly summarize BRCA1s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in ... Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, ... Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing ... Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers. ...
BRCA1 Associated Protein, BRAP2 (Impedes mitogenic signal propogation; IMP) is mainly cytoplasmic and binds to the NLS motifs ... BRAP2 may function as a cytoplasmic retention protein and play a role in regulating transport of nuclear proteins. More ... Epigenetics and Nuclear Signaling DNA / RNA DNA Damage & Repair DNA Damage Response BRCA1 ... Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex miRNA assays. By ...
... which is inhibited by BRCA1-associated protein 1 (BAP1). The sites at which other BRCA1-interacting proteins bind are also ... BRCA1 exists as a stable heterodimer through its RING-mediated interaction with BRCA1-associated RING domain protein 1 (BARD1 ... The human breast and ovarian cancer type 1 susceptibility gene (BRCA1) encodes a protein of 1,863 amino acids. BRCA1 has two ... BACH1, BRCA1-interacting protein carboxy-terminal helicase 1; CtIP, CtBP-interacting protein; NLS, nuclear localization ...
K63-linked polyubiquitin modification-dependent protein binding Source: InterPro. View the complete GO annotation on QuickGO ... BRCA1-A complex subunit RAP80. BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... K63-linked polyubiquitin modification-dependent protein binding Source: InterPro. View the complete GO annotation on QuickGO ...
In conclusion, our results suggest that variants Y1703S, W1718L and G1770V can be classified as likely pathogenic BRCA1 ... The TA assay shows that variants Y1703S, W1718L and G1770V dramatically compromise the transcriptional activity of BRCA1, while ... located in the C-terminal region of BRCA1 by combining in silico prediction tools and structural analysis with a transcription ... Germline inactivating mutations in BRCA1 and BRCA2 genes are responsible for Hereditary Breast and Ovarian Cancer Syndrome ( ...
CREB-binding protein has been shown to interact with: TF2, AR, AIRE, BRCA1, C-jun, CSK, Ccaat-enhancer-binding proteins, CDX2, ... CREB-binding protein, also known as CREBBP or CBP, is a protein that in humans is encoded by the CREBBP gene. The CREB protein ... First isolated as a nuclear protein [Ref] that binds to cAMP-response element-binding protein (CREB), this gene is now known to ... Zhang Q, Vo N, Goodman RH (July 2000). "Histone binding protein RbAp48 interacts with a complex of CREB binding protein and ...
Michael Yaffe on Phosphoserine/threonine binding domains: molecular integrators of protein kinase signaling in cell cycle ... Cancer-associated mutations in BRCA1 BRCT. *Eliminating phosphopeptide binding function. *ATM amplification involves H2AX ... Fundamentals of protein chromatography: basic protein pur... Fundamentals of protein chromatography: basic protein purification ... Fuzzy protein theory for disordered proteins Fuzzy protein theory for disordered proteins ...
RAD50 double strand break repair protein. hRad50, RAD50-2. 5q31.1. RBBP8 RB binding protein 8, endonuclease. SCKL2. CtIP, RIM, ... BRCA1 BRCA1, DNA repair associated. RNF53, BRCC1, PPP1R53, FANCS. 17q21.31. MRE11 MRE11 homolog, double strand break repair ... BRCA1 C complex: BRCA1 forms a complex with RBBP8 and MRN (MRE11/RAD50/NBN) in a cell cycle-dependent manner during S and G2 ... The MRN complex also has other functions not related to its role in the BRCA1 C complex. RBBP8 is required for DNA end ...
Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD (May 1997). "BRCA1 is a component of the RNA ... Sp1 and cAMP-response-element-binding protein-binding protein (CBP/p300)". Biochem. J. 339 (3): 751-8. doi:10.1042/0264-6021: ... The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box ... gene is mediated by interactions of Msx1 protein with a multi-protein transcriptional complex containing TATA-binding protein, ...
... death-associated protein kinase; DDB, damage specific DNA binding proteins 1 and 2; DNA-PK, DNA-dependent protein kinase; DRAM ... 2000). BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. ... GATA Binding Protein 4; HDAC, histone deacetylases; HMGB1, High Mobility Group Box 1; HP1α, heterochromatin protein 1α; HR, ... 2007). p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. ...
Kim, H., Chen, J., and Yu, X. (2007). Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316 ... The BRCA1 protein is a RING finger domain containing E3 ubiquitin ligase. H2A and H2B were identified as BRCA1 substrates in an ... BRCA1. Inactivation of tumor suppressor BRCA1 leads to breast and ovarian cancer. Female individuals carrying a mutated BRCA1 ... Another RING finger containing protein BARD1, which carries an enzyme dead mutation in its RING finger, binds to BRCA1 and ...
2007) Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316, 1202-1205. ... regulatory-associated protein of mTOR. Raptor. mammalian LST8/G-protein β-subunit like protein. mLST8/GβL. rapamycin- ... BCA Protein Assay kit (Pierce, Rockford, IL) was used to determine protein concentration. 10-15 μg of protein was subjected to ... 2000) CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells. Cell Microbiol. 2, 19 ...
The BRCA1 C-terminal (BRCT) domain has recently been implicated as a phospho-protein binding domain. We demonstrate here that a ... DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal ... DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal ... DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal ...
... bound only to wild-type BRCA1 protein but not to the BRCA1-BRCT mutant (Supplementary Fig. S5), was expressed in Brca1tr/tr ... The BRCA1 BRCT domains are phospho-protein binding motifs that are important for the tumor suppressor function of BRCA1 ( 4- 6 ... The BRCA1-BRCT domains bind to phosphorylated AKT (pAKT) and lead to its ubiquitination toward protein degradation. BRCA1 ... AKT can phosphorylate BRCA1 ( 12), implying that AKT may bind to BRCA1 directly. Both AKT and BRCA1 regulate the cell cycle and ...
Rabbit polyclonal BRCA1 (phospho S1423) antibody. Validated in WB, IHC and tested in Human. Immunogen corresponding to ... The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif ... The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates ... Note=Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer.. Defects in BRCA1 ...
  • Inherited mutations in BRCA1 predispose to breast and ovarian cancer, but the biological function of the BRCA1 protein has remained largely elusive. (nih.gov)
  • Furthermore, it is unknown whether cancer-associated BAP1 mutations affect protein function. (aacrjournals.org)
  • In this study, we sought to characterize the in vivo growth suppression phenotype of BAP1, to determine if it was a genuine tumor suppressor, to ask whether the mutations found in cancer cells inactivated protein function, and to ask whether BAP1 exerted its tumor suppressor activity through the BRCA1 pathway. (aacrjournals.org)
  • Strikingly, within some of these genes in BRCA1 null breast tumors, there are specific insertion/deletion mutations located close to R-loop-mediated BRCA1 binding sites within TRs. (nih.gov)
  • Mutations of BRCA1 are found in a high percentage of hereditary breast and ovarian cancers [ 1 ]. (mdpi.com)
  • Important clinical mutations routinely used in research settings are indicated, such as Cys61Gly and Cys64Gly, which target the RING domains, and Met1775Arg, which disrupts the BRCA1 BRCT domain interaction with phosphorylated proteins and the accumulation of BRCA1 at damage-induced foci. (nih.gov)
  • Germline inactivating mutations in BRCA1 and BRCA2 genes are responsible for Hereditary Breast and Ovarian Cancer Syndrome (HBOCS). (plos.org)
  • In conclusion, our results suggest that variants Y1703S, W1718L and G1770V can be classified as likely pathogenic BRCA1 mutations. (plos.org)
  • Mutations in BRCA1 and BRCA2 genes confer high lifetime risks of breast and ovarian cancer, among other neoplasias [2] , [3] . (plos.org)
  • Most BRCA1 mutations cause truncated BRCA1 gene products that lack one or both COOH-terminal BRCT domains. (aacrjournals.org)
  • Clinically relevant missense mutations identified at the COOH terminus of BRCA1 abolish the BRCT structure ( 1 , 2 ), and Brca1 deficiency leads to tumor formation in mice ( 5 ). (aacrjournals.org)
  • Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics . (wikipedia.org)
  • B) A sequence-function map of the effect of missense mutations in the BRCA1 RING domain on E3 ligase function. (genetics.org)
  • 3-6 Other cancers also show elevated incidence of mutations in BRCA1 (melanoma and testicular) and BRCA2 (male breast cancer, prostate cancer and pancreatic cancer). (bmj.com)
  • This protein may be the target of oncogenic mutations in breast or ovarian cancer. (cancerindex.org)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Inherited mutations in particular genes, such as BRCA1 , BRCA2 , and HOXB13 , account for some cases of hereditary prostate cancer. (medlineplus.gov)
  • Rebbeck TR, Mitra N, Wan F et al (2015) Association of type and location of BRCA1 and BRCA2 mutations with risk of breastand ovarian cancer. (springer.com)
  • Ruffner H, Joazeiro CA, Hemmati D et al (2001) Cancer-predisposing mutations within the RING domain of BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. (springer.com)
  • Inherited mutations in the BRCA1 gene predispose to a higher risk of breast/ovarian cancer. (hindawi.com)
  • BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways. (hindawi.com)
  • in healthy cells it functions to maintain proper genomic repair and cell division, but inherited mutations in the BRCA1 gene encode altered forms of the protein that contribute to development of breast and ovarian cancer [ 2 - 4 ]. (hindawi.com)
  • BRCA1 gene mutations disrupt these processes and result in chromosome instability and defective checkpoints that accelerate cellular transformation [ 6 - 8 ]. (hindawi.com)
  • We have compared the transcriptomes of primary breast and ovarian epithelial cultures from patients predisposed to cancer, bearing monoallelic BRCA1 or BRCA2 mutations, with corresponding cultures from control individuals. (aacrjournals.org)
  • Eligible cases included unaffected at-risk women in the Fox Chase Family Risk Assessment Program who were shown to be carriers of BRCA1 or BRCA2 mutations. (aacrjournals.org)
  • This mechanism can help explain resistance to a promising chemotherapy called PARP inhibition seen in patients and mouse models with BRCA1 mutations. (innovations-report.com)
  • The discovery that mutations in the BRCA1 gene predispose individuals to an increased risk of developing breast or ovarian cancer has prompted the search for what the normal BRCA1 protein does in the cell. (sciencemag.org)
  • Intriguingly, BRG1 binds to BRCA1 within the region encoded by exon 11, the section of the BRCA1 gene that harbors many of the predisposing cancer mutations identified so far. (sciencemag.org)
  • Now the search is on for mutations in BRG1 and other SWI/SNF proteins that also might predispose to cancer. (sciencemag.org)
  • Protein stability versus function: effects of destabilizing missense mutations on BRCA1 DNA repair activity. (sigmaaldrich.com)
  • Mutations in breast cancer susceptibility gene BRCA1 (breast cancer early-onset 1) are associated with increased risk of developing breast and ovarian cancers. (sigmaaldrich.com)
  • We found that all of the mutations, regardless of how profound their destabilizing effects, retained some DNA repair activity and thereby partially rescued the chicken BRCA1 knockout. (sigmaaldrich.com)
  • Why BRCA1 and BRCA2 germline mutations predispose to breast and ovarian cancer, rather than other tumor types, is under investigation. (mskcc.org)
  • We identified OSE proteins with altered expression derived from women with a family history (FH) of ovarian and/or breast cancer and mutations in the BRCA1 tumor suppressor gene. (mcponline.org)
  • Early onset familial ovarian cancer is often associated with loss of heterozygosity localized to chromosome 17q ( 7 ) and germ line mutations in the breast cancer antigen-1 ( BRCA1 ) gene ( 8 ). (mcponline.org)
  • Cancers with mutations in genes encoding proteins involved in DNA repair may be more sensitive to treatments that induce synthetic lethality by inducing DNA damage or inhibiting complementary DNA repair mechanisms. (aacrjournals.org)
  • Patients with breast or ovarian cancer with mutations of BRCA1 have been treated with inhibitors of PARP with early clinical success ( 5 ). (aacrjournals.org)
  • Our findings suggest that certain mutations in the BRCA1 gene may put people at increased risk for metabolic diseases like obesity and type 2 diabetes," said Dr. Spangenburg. (eurekalert.org)
  • The discovery that it is linked to mutations in BRCA1 in certain families transformed this view, and since that time, mutations in several genes involved in BRCA1 -related pathways have also been associated with breast cancer susceptibility. (healthcanal.com)
  • Many of these mutations eliminate the phosphopeptides-binding function of the tandem BRCT domains, preventing propogation of the DNA damage signal. (mit.edu)
  • The findings, conducted in cell culture and in mice and reported by the researchers in the January issue of Molecular Endocrinology, could help explain why women who have mutations in their BRCA1 gene are susceptible to a number of different "hormone-dependent" cancers, including those of the breast, endometriun and cervix. (innovations-report.com)
  • Al-Sukhni W, Rothenmund H, Borgida AE et al (2008) Germline BRCA1 mutations predispose to pancreatic adenocarcinoma. (springer.com)
  • Amir RE, Van den Veyver IB, Wan M et al (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. (springer.com)
  • [10] Mutations in the BARD1 protein that affect its structure appear in many breast , ovarian , and uterine cancers , suggesting the mutations disable BARD1's tumor suppressor function. (wikipedia.org)
  • The breast cancers arising in women with BRCA1 mutations are mostly classified as "triple-negative", lacking expression of the estrogen receptor, the progesterone receptor, and the HER2 gene. (healthcanal.com)
  • The highlighted domain has been suggested to be the result of an internal duplication, each of the tandem domains being designated as a 'BRCT domain' (for BRCA1 C-terminus). (nih.gov)
  • The BRCT domain is not limited to the C-termini of protein sequences and can be found in multiple copies or in a single copy as in RAP1 and TdT, suggesting that it could well constitute an autonomous folding unit of approx. (nih.gov)
  • It also contains a BRCT C-terminal domain, an approximately 100 amino acid tandem repeat, which appears to act as a phospho-protein binding domain [ PMID: 14576433 ]. (ebi.ac.uk)
  • The BRCT domain is a phospho-protein binding domain. (ebi.ac.uk)
  • The BRCA1 protein contains an N -terminal really interesting new gene (RING) finger domain and two BRCA1 C -Terminal (BRCT) domains, which are involved in various protein-protein interactions [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. (mdpi.com)
  • BRCA1 has two highly conserved motifs at its termini: the RING domain and tandem BRCT domains. (nih.gov)
  • The RING domain sequence encodes a folded protein structure and confers the E3 ubiquitin ligase activity of BRCA1, and the BRCT domains bind phosphorylated proteins that are primarily involved in the DNA damage response. (nih.gov)
  • BRCA1 forms a complex with RBBP8 and MRN (MRE11/RAD50/NBN) in a cell cycle-dependent manner during S and G2 phase of the cell cycle through the BRCT domains of BRCA1 binding to phosphorylated S327, a CDK phosphorylation site of RBBP8 in a phospho-SPxF motif. (genenames.org)
  • The BRCA1 C-terminal (BRCT) domain has recently been implicated as a phospho-protein binding domain. (asm.org)
  • We demonstrate here that a CTBP-interacting protein CtIP interacts with BRCA1 BRCT domains in a phosphorylation-dependent manner. (asm.org)
  • The BRCA1-BRCT domains bind to phosphorylated AKT (pAKT) and lead to its ubiquitination toward protein degradation. (aacrjournals.org)
  • BRCA1 mutant cells lacking the BRCT repeats accumulate nuclear pAKT and consequently inactivate the transcription functions of FOXO3a, a main nuclear target of pAKT. (aacrjournals.org)
  • The BRCA1 BRCT domains are phospho-protein binding motifs that are important for the tumor suppressor function of BRCA1 ( 4 - 6 ). (aacrjournals.org)
  • the Znf C3HC4- RING domain , the BRCA1 serine domain and two BRCT domains. (wikipedia.org)
  • 18 The aminoterminus of NBS1 exhibits a forkhead associated (FHA) domain, followed by a BRCA1 carboxyterminal (BRCT) domain. (bmj.com)
  • In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. (cancerindex.org)
  • BRCT domains are protein modules mainly found in Eukaryota. (eu.org)
  • BRCT domains are present in proteins that are associated with DNA damage response. (eu.org)
  • This phospho-protein mediated interaction of the BRCT domain has a central role in cell-cycle check point and DNA repair functions. (eu.org)
  • The LIG_BRCT_BRCA1_1 motif binds with low affinity to the BRCT domain of BRCA1. (eu.org)
  • The motif has the consensus sequence S..F and these residues are specially recognized by the binding pocket in the BRCT domains. (eu.org)
  • BRCT domains were first identified in and named after the breast cancer susceptibility protein BRCA1 ( Zhang,1999 ). (eu.org)
  • An unusual feature of paired BRCT motifs is that the phosphopeptides bind across the domain-domain interface ( Clapperton,2004 ). (eu.org)
  • Also, a poorly characterised motif binding the TopBP1 BRCT may match the pattern S.II but more data is needed ( Liu,2003 ). (eu.org)
  • Since consensus motifs have so far been defined for just a few BRCT domains, the range of different binding motif patterns could be quite large. (eu.org)
  • BRCT repeats as phosphopeptide-binding modules involved in protein targeting. (eu.org)
  • Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. (eu.org)
  • Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. (eu.org)
  • Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. (eu.org)
  • Manke IA, Lowery DM, Nguyen A et al (2003) BRCT repeats as phosphopeptide-binding modules involved in protein targeting. (springer.com)
  • Rodriguez M, Yu X, Chen J et al (2003) Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. (springer.com)
  • Yu X, Chini CC, He M et al (2003) The BRCT domain is a phospho-protein binding domain. (springer.com)
  • Kim H, Huang J, Chen J (2007) CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response. (springer.com)
  • Yu X, Wu LC, Bowcock AM et al (1998) The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression. (springer.com)
  • The RING and BRCT protein interaction domains are shown at the amino and carboxy termini, respectively. (hindawi.com)
  • BRCA1 is a large protein of 1863 residues with two small structured domains at its termini: a RING domain at the N-terminus and a BRCT (BRCA1 C-terminus domain) repeat domain at the C-terminus. (sigmaaldrich.com)
  • In the present study, we ask whether and how reduced thermodynamic stability of the isolated BRCT mutants translates into loss of function of the full-length protein in the cell. (sigmaaldrich.com)
  • It is likely that both protein context (location of the BRCT domains at the C-terminus of the large BRCA1 protein) and cellular environment (binding partners, molecular chaperones) buffer these destabilizing effects such that at least some mutant protein is able to adopt the folded functional state. (sigmaaldrich.com)
  • The BRCA1 breast cancer gene contains a tandem pair of BRCT domains that function together a unit to bind to specific phosphorylated proteins involved in detection and repair of DNA damage. (mit.edu)
  • However, disruption of the tandem BRCT domains of BRCA1 that our lab has identified may allow tumor cells to be more susceptible to anti-cancer drugs. (mit.edu)
  • 53BP1 contains two breast cancer susceptibility gene 1 COOH terminus (BRCT) motifs, which are present in several proteins involved in DNA repair and/or DNA damage-signaling pathways. (rupress.org)
  • BARD1 shares homology with the two most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. (wikipedia.org)
  • [13] BARD1 tandem BRCA1 C-terminus (BRCT) motifs fold into a binding pocket with a key lysine residue (K619), and bind to poly(ADP-ribose) (PAR), which targets the BRCA1/BARD1 heterodimer to damaged DNA sites. (wikipedia.org)
  • BRCA1 is a breast cancer susceptibility gene that is down-regulated in a significant proportion of sporadic breast cancers. (edu.au)
  • However, estrogen has also been shown to induce the expression of the tumor suppressor gene, BRCA1 . (biomedcentral.com)
  • Interestingly, the BRCA1 gene lacks a consensus estrogen response element. (biomedcentral.com)
  • p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence. (uniprot.org)
  • section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. (uniprot.org)
  • BRCA1 (em inglês, breast cancer 1, early onset ) é um gene humano pertencente a classe dos genes supressores de tumor conservado nos mamíferos é responsável pela síntese da proteína de mesmo nome BRCA1. (wikipedia.org)
  • [ 1 ] Foi primeiramente mencionado como um gene localizado na região 21 do braço longo do cromossomo 17 (17q21) em 1990 pelo laboratório da professora Mary-Claire King , porém somente em 1994 o gene BRCA1 foi devidamente identificado pelo grupo do professor Mark Skolnick da Universidade de Utah através da realização de clonagem do gene BRCA1 . (wikipedia.org)
  • Mutações no gene BRCA1 em células germinativas tem sido associada a um aumento significativo da predisposição ao câncer de mama e de ovário . (wikipedia.org)
  • Localização citogenética do gene BRCA1 no cromossomo 17. (wikipedia.org)
  • O gene BRCA1 codifica uma proteína de 1863 aminoácidos denominada BRCA1. (wikipedia.org)
  • Logo após a identificação do BRCA1 vários pesquisadores passaram a realizar estudos, em diversas populações, visando a identificação das mutações associadas a esse gene. (wikipedia.org)
  • Nessa população foi encontrado duas mutações associadas ao gene BRCA1 , uma deleção dos nucleotídeos AG na posição 185 e uma inserção de uma C na posição 5382, e uma mutação associada ao gene BRCA2 . (wikipedia.org)
  • Atualmente as mutações encontradas no gene BRCA1 são inúmeras e são encontradas ao longo de toda a sua sequência codificadora espalhada em seus 24 exons. (wikipedia.org)
  • BAP1 is a DUB originally identified as a protein interacting with the RING finger domain of the breast cancer susceptibility gene product BRCA1 ( 3 ). (aacrjournals.org)
  • PALB2 (partner and localizer of BRCA2) is also a breast cancer susceptibility gene ( 11 - 13 ) and was first identified by its interaction with BRCA2 protein ( 14 ). (aacrjournals.org)
  • The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. (mdpi.com)
  • Subsequently, the BRCA1 gene was cloned and analyzed to be composed of 22 coding exons distributed over ~100 kb of genomic DNA [ 4 , 5 ]. (mdpi.com)
  • The BRCA1 gene is conserved in mammals [ 21 , 22 ] and the BRCA1 protein has roles in various cellular events including cell cycle control, DNA damage signaling, maintaining genomic integrity, protein ubiquitination, and transcriptional regulation. (mdpi.com)
  • The human breast and ovarian cancer type 1 susceptibility gene ( BRCA1 ) encodes a protein of 1,863 amino acids. (nih.gov)
  • CREB-binding protein, also known as CREBBP or CBP, is a protein that in humans is encoded by the CREBBP gene. (wikipedia.org)
  • First isolated as a nuclear protein [Ref] that binds to cAMP-response element-binding protein (CREB), this gene is now known to play critical roles in embryonic development, growth control, and homeostasis by coupling chromatin remodeling to transcription factor recognition. (wikipedia.org)
  • The protein encoded by this gene has intrinsic histone acetyltransferase activity and also acts as a scaffold to stabilize additional protein interactions with the transcription complex. (wikipedia.org)
  • Recent results suggest that novel CBP-mediated post-translational N-glycosylation activity alters the conformation of CBP-interacting proteins, leading to regulation of gene expression, cell growth and differentiation, Homeodomain interacting protein kinase 2 (HIPK2) phosphorylates several regions of CBP close to the N-terminal and close to the C-terminal region as well. (wikipedia.org)
  • As one of the few proteins in the preinitiation complex that binds DNA in a sequence-specific manner, it helps position RNA polymerase II over the transcription start site of the gene. (wikipedia.org)
  • The binding of TBP to these promoters is facilitated by housekeeping gene regulators. (wikipedia.org)
  • Binding of TFIID to the TATA box in the promoter region of the gene initiates the recruitment of other factors required for RNA Pol II to begin transcription. (wikipedia.org)
  • The breast cancer susceptibility gene 1 ( BRCA1 ) plays a key role in mammary tumorigenesis. (aacrjournals.org)
  • However, the reasons why silencing the Brca1 gene leads to tumorigenesis are not clearly understood. (aacrjournals.org)
  • Mutation of Brca1 gene increases the phosphorylation and the kinase activity of AKT. (aacrjournals.org)
  • The breast cancer susceptibility gene 1 ( Brca1 ) has been shown to play a key role in both hereditary and sporadic mammary tumorigenesis ( 1 - 3 ). (aacrjournals.org)
  • Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 ( / ˌ b r æ k ə ˈ w ʌ n / ) gene . (wikipedia.org)
  • The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map) . (wikipedia.org)
  • The protein encoded by this ubiquitously expressed gene interacts with the tumor suppressing BRCA1 (breast cancer 1) protein and and the ATM (ataxia telangiectasia mutated) protein. (genecards.org)
  • The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. (genecards.org)
  • BRAT1 (BRCA1 Associated ATM Activator 1) is a Protein Coding gene. (genecards.org)
  • GO annotations related to this gene include binding . (genecards.org)
  • Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS).Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours.For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. (nih.gov)
  • For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. (nih.gov)
  • This gene encodes a protein which interacts with the N-terminal region of BRCA1. (cancerindex.org)
  • What does this gene/protein do? (cancerindex.org)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • The BRCA1 protein, a hereditary breast and ovarian cancer-causing gene product, is known as a multifunctional protein that performs various functions in cells. (springer.com)
  • Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. (springer.com)
  • O'Donovan PJ, Livingston DM (2010) BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. (springer.com)
  • Wu LC, Wang ZW, Tsan JT et al (1996) Identification of a RING protein that can interact in vivo with the BRCA1 gene product. (springer.com)
  • This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. (creativebiomart.net)
  • BRCA1 is a breast and ovarian cancer-suppressing gene and a major contributor to genome integrity control. (aacrjournals.org)
  • BRCA1 has structural motifs characteristic of transcription factors, and it increases the expression of certain genes including the master tumor suppressor gene, p53 . (sciencemag.org)
  • that BRCA1 is a crucial component of SWI/SNF, an 18-protein complex that remodels chromatin, now suggests how BRCA1 might regulate gene transcription. (sciencemag.org)
  • One pathway involves the BRCA1 'breast cancer gene', so deepens scientists' understanding of how cancer develops and could one day lead to new treatments for the disease. (cancerresearchuk.org)
  • When CtIP becomes activated, say the scientists, it causes the protein made by the BRCA1 gene to bind to the damaged DNA. (cancerresearchuk.org)
  • Identification of these and other OSE proteins may be useful in detecting changes suggestive of increased risk of developing preneoplastic disease and defining the possible role(s) of the BRCA1 gene in regulation of OSE cell function. (mcponline.org)
  • HDACs catalyze the removal of acetyl groups from histone and nonhistone proteins alike, altering gene expression and protein stability/function, respectively ( 13 ). (aacrjournals.org)
  • gene name abbreviated RB or RB1 ) is a tumor suppressor protein that is dysfunctional in several major cancers . (wikipedia.org)
  • In humans, the protein is encoded by the RB1 gene located on chromosome 13-more specifically, 13q14.1-q14.2 . (wikipedia.org)
  • If both alleles of this gene are mutated early in life, the protein is inactivated and results in development of retinoblastoma cancer, hence the name Rb . (wikipedia.org)
  • This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. (nih.gov)
  • We believe that the significance of the BRCA1 gene goes well beyond breast cancer risk. (eurekalert.org)
  • This is the first evidence since the discovery of BRCA1 in 1994 that the gene is expressed in human muscle cells. (eurekalert.org)
  • They further established that the protein produced by the BRCA 1 gene binds with a protein known to play an important role in the metabolism of fat in muscle cells known as Acetyl-CoA carboxylase or ACC. (eurekalert.org)
  • This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. (jax.org)
  • NF1-X binds to the promoter for the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase gene [ PMID: 10432316 ]. (ebi.ac.uk)
  • Researchers at the Perelman School of Medicine at the University of Pennsylvania and the University of Oulu, Finland, published their discovery of a mutation in the Abraxas gene, which interacts with the well-known breast-cancer gene BRCA1 , in Science Translational Medicine this week. (healthcanal.com)
  • Taken together, these observations suggest that the Abraxas mutation keeps the Abraxas protein from migrating with its binding partners at sites where DNA repair is needed, and establishes Abraxas as a breast cancer susceptibility gene. (healthcanal.com)
  • A new mechanism for the breast cancer gene BRCA1. (mit.edu)
  • 2. The tumor suppressor gene that codes for this protein. (thefreedictionary.com)
  • It s been known that the breast cancer susceptibility gene BRCA1 regulates use of estrogen in breast and other cells, but now researchers at Georgetown University Medical Center have discovered that it also controls activity of a second sex steroid hormone, progesterone. (innovations-report.com)
  • It also has implications for ordinary cancers that arise because a normal BRCA1 gene is under-expressed, said the study s principal investigator, Eliot Rosen, MD, PhD, professor of oncology, cell biology, and radiation medicine at the Lombardi Comprehensive Cancer Center. (innovations-report.com)
  • The BRCA1 gene and a second gene, BRCA2, were discovered to be breast cancer susceptibility genes in 1994 and 1995, respectively. (innovations-report.com)
  • Rosen and his research team undertook the study to understand why loss of the BRCA1 gene results in cancers in tissues that are dependent on hormones. (innovations-report.com)
  • In one set of cell culture studies in the laboratory, they used breast cancer cells that were responsive to progesterone, and then genetically manipulated them to either over or under-express the BRCA1 gene in order to assess the gene s effect on progesterone receptor signaling. (innovations-report.com)
  • They also used mice in which the BRCA1 gene was partially deleted, but only in breast tissue. (innovations-report.com)
  • Trabectedin induces double strand breaks and that the BRCA1-/- human cell line HCC1937 and BRCA2Δ22/Δ22 mice cells are more sensitive to trabectedin and this hypersensitivity is reverted by complementation by the BRCA1 or BRCA2 gene. (knowcancer.com)
  • RNA-binding proteins (RBPs) are effectors and regulators of posttranscriptional gene regulation (PTGR). (springer.com)
  • BRCA1 and c-Myc associate to transcriptionally repress psoriasin, a DNA damage-inducible gene. (prolekare.cz)
  • BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene . (wikipedia.org)
  • New Brunswick, N.J. - Studies have well established that women who harbor a mutation in the BRCA1 tumor suppressor gene are at greater risk for developing breast and ovarian cancers. (healthcanal.com)
  • It is a mutated form of this gene that investigators explored in this latest research ( 53bp1 Loss Rescues BRCA1 Deficiency and is Associated with Triple-Negative and BRCA-Mutated Breast Cancers), which is published in the current online edition of Nature Structural & Molecular Biology . (healthcanal.com)
  • Women with a BRCA1 mutation have one normal copy of the gene inherited from one parent, and one mutant copy inherited from the other parent. (healthcanal.com)
  • The cancers that arise lose the normal copy, thus also losing all tumor-suppressing function of the BRCA1 gene. (healthcanal.com)
  • Há também o domínio chamado Coiled Coil em BRCA1, por meio do qual este interage com BRCA2 por intermédio da proteínas PALB2 (partner and localizer of BRCA2) durante o reparo por recombinação homólogo. (wikipedia.org)
  • Espectro de mutações deletérias em BRCA1 (n=57) e BRCA2 (n=56) em mulheres jovens com câncer de mama unilateral (em amarelo) e contralateral (em vermelho). (wikipedia.org)
  • BRCA1 and BRCA2 are prominently associated with inherited breast and ovarian cancer. (aacrjournals.org)
  • The encoded proteins function in DNA damage responses, but no functional link between BRCA1 and BRCA2 has been established. (aacrjournals.org)
  • We show here that PALB2 physically and functionally connects BRCA1 and BRCA2 into a DNA damage response network that also includes the RAD51 recombinase. (aacrjournals.org)
  • Furthermore, PALB2 independently interacts with BRCA1 and BRCA2 through its NH 2 and COOH termini, respectively. (aacrjournals.org)
  • Using extracts from these cells, we find that PALB2 mediates the physical interaction of BRCA2 with a COOH-terminal fragment of BRCA1. (aacrjournals.org)
  • Analysis of the assembly of foci in these cells by BRCA1, PALB2, BRCA2, and RAD51 suggests that BRCA1 recruits PALB2, which in turn organizes BRCA2 and RAD51. (aacrjournals.org)
  • Resistance to mitomycin C and the repair of DNA double-strand breaks by homologous recombination require the interaction of PALB2 with both BRCA1 and BRCA2. (aacrjournals.org)
  • These results suggest that BRCA1 and BRCA2 cooperate in DNA damage responses in a PALB2-dependent manner, and have important implications for the genesis of breast/ovarian cancer and for chemotherapy with DNA interstrand cross-linking agents. (aacrjournals.org)
  • BRCA1 and BRCA2 are the major genes associated with inherited susceptibility to breast and ovarian cancer ( 1 - 4 ). (aacrjournals.org)
  • These observations suggest that BRCA1 and BRCA2 function in cellular responses to DNA damage. (aacrjournals.org)
  • Importantly, BRCA1 and BRCA2 have not been functionally linked (reviewed in refs. (aacrjournals.org)
  • Although it has been reported that BRCA1 and BRCA2 coimmunopurify ( 8 - 10 ), the interaction may be indirect and may involve only a small proportion of either protein ( 6 , 7 ). (aacrjournals.org)
  • Importantly, numerous BRCA2-dependent functions require the capacity of PALB2 to interact with both BRCA1 and BRCA2, including the assembly of BRCA2 foci, the assembly of RAD51 foci, HR, and resistance to MMC. (aacrjournals.org)
  • These results show that BRCA1, PALB2, BRCA2, and RAD51 function in a DNA damage response pathway that culminates in HR. Together, our results suggest that PALB2 serves as a physical and functional linker between BRCA1 and BRCA2. (aacrjournals.org)
  • Thus, genetic analysis of BRCA1 and BRCA2 is a cornerstone of genetic counseling practice. (plos.org)
  • However, classification of genetic variants as pathogenic is challenging, particularly for missense changes and for silent or intronic variants that cannot be directly associated with increased cancer risk and are classified as variants of uncertain significance (VUS), which are found in 13% of BRCA1 and BRCA2 genetic tests [5] . (plos.org)
  • Diverse multifactorial likelihood algorithms have been developed and applied for both BRCA1 and BRCA2 variants (reviewed in Spurdle et al. (plos.org)
  • Therefore, functional analyses that assess specific properties of BRCA1 or BRCA2 may help to classify VUS [7] . (plos.org)
  • BRCA1 and BRCA2 are unrelated proteins, [10] but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA , or destroy cells if DNA cannot be repaired. (wikipedia.org)
  • [11] [12] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation , damaged DNA is not repaired properly, and this increases the risk for breast cancer . (wikipedia.org)
  • BRCA1 is unrelated to BRCA2 , i.e. they are not homologs or paralogs . (wikipedia.org)
  • Mutation of BRCA1 and BRCA2 is the most common cause of inherited breast and ovarian cancer. (bmj.com)
  • Functional assays provide an important alternative for classification of BRCA1 and BRCA2 VUS. (bmj.com)
  • Progress in implementing functional assays to assess missense variants of BRCA1 and BRCA2 is considered here, along with current limitations and the path to more impactful assay systems. (bmj.com)
  • While functional assays have been developed to independently evaluate BRCA1 and BRCA2 VUS, high-throughput assays with sufficient sensitivity to characterise the large number of identified variants are lacking. (bmj.com)
  • Additionally, because of relatively low conservation of certain domains of BRCA1, and of BRCA2, between humans and rodents, heterologous expression in rodent cells may have limited reliability or capacity to assess variants present throughout either protein. (bmj.com)
  • In the 1990s, pathogenic variants in BRCA1 and BRCA2 were found to be associated with hereditary breast and ovarian cancer (HBOC). (bmj.com)
  • 1 2 Among genes associated with HBOC, BRCA1 and BRCA2 confer the highest lifetime risks of these cancers and are the most frequently mutated genes in women with HBOC. (bmj.com)
  • Genetic testing for pathogenic variants in BRCA1 , BRCA2 and other cancer susceptibility genes is recommended for individuals with a strong family and/or personal history of HBOC (see figure 1 ), since risk preventative strategies improve outcomes. (bmj.com)
  • Indeed, individuals who carry a pathogenic variant in BRCA1 and BRCA2 are recommended to consider prophylactic surgeries including bilateral risk-reducing mastectomy (RRM) and/or risk-reducing bilateral salpingo-oophorectomy (rrBSO). (bmj.com)
  • Identification of candidate cancer predisposing variants by performing whole-exome sequencing on index patients from BRCA1 and BRCA2-negative breast cancer families. (cancerindex.org)
  • The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. (medlineplus.gov)
  • For this reason, the BRCA1 and BRCA2 proteins are considered to be tumor suppressors, which means that they help keep cells from growing and dividing too fast or in an uncontrolled way. (medlineplus.gov)
  • Venkitaraman AR (2014) Cancer suppression by the chromosome custodians, BRCA1 and BRCA2. (springer.com)
  • We report here on the transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1 and BRCA2 mutation carriers and controls. (aacrjournals.org)
  • With this rationale in mind, we have undertaken an investigation of two of the most common predisposing genes, BRCA1 ( 10 , 11 ) and BRCA2 (refs. (aacrjournals.org)
  • BRCA2 is the major mediator protein for Rad51 function in mammalian cells, directly binding Rad51, which is required for normal Rad51 function in cells. (mskcc.org)
  • Rad52 function appears to be dispensable unless the BRCA2 protein is inactivated, when Rad52 becomes vital for cell survival. (mskcc.org)
  • Inactivation of the BRCA1-BRCA2 pathway occurs in sporadic breast cancer as well as germline mutation carriers. (mskcc.org)
  • Part of the RAD21 paralog protein complex CX3 which acts in the BRCA1-BRCA2-dependent HR pathway. (nih.gov)
  • Rad51 also interacts with products of two genes implicated in susceptibility to breast cancer, BRCA1 and BRCA2. (clontech.com)
  • In particular, BRCA2 protein is shown to regulate both the intracellular localization and DNA-binding ability of Rad51. (clontech.com)
  • Particularly, the link between the BRCA1/BRCA2 tumor-suppressor genes and hereditary breast cancer is well established ( 3 , 4 ), but the role of these genes in nonfamilial cancers remains unclear. (aacrjournals.org)
  • Also known as BRCA1-A complex subunit BRE (BRCA1/BRCA2-containing complex subunit 45) (Brain and reproductive organ-expressed protein). (mybiosource.com)
  • The two susceptibility genes associated with epithelial-type OC are BRCA1 and BRCA2. (knowcancer.com)
  • The discovery of BRCA1 and BRCA2 ( BRCA 1/2) is among the most important discoveries in human cancer genetics. (aacrjournals.org)
  • HuR is an RNA binding protein implicated in posttranscriptional regulation of many genes and is overexpressed in sporadic breast cancer. (edu.au)
  • Results Eighty-five genes involved in DNA repair, mitotic checkpoint, nucleosome assembly, and the BRCA1 network were differentially regulated by CtBP2 expression. (edu.au)
  • The consequences of aberrant DNA methylation at specific transcription factor motifs, along with the multiple mutational events that can occur in a variety of essential genes such as BRCA1, paint a complex picture where both genetic and epigenetic changes contribute to tumour formation. (nih.gov)
  • Estrogens enhance transcription of target genes by stimulating the association of the estrogen receptor (ER) and related coactivators to estrogen response elements or to transcription complexes formed at activator protein (AP)-1 or specificity protein (Sp)-binding sites. (biomedcentral.com)
  • Genome-wide analysis revealed widespread BRCA1 binding enrichment at R-loop-rich termination regions (TRs) of actively transcribed genes. (nih.gov)
  • As the protein products of the genes so far indicated are central players in the pathways involved in cell cycle checkpoint functions and in the sensing, transduction, and repair of DNA lesions, 5 other similarly acting genes may represent new potential candidates for breast and/or ovarian cancer susceptibility. (bmj.com)
  • When patients were categorised into groups based on mRNA expression levels of each biomarker (i.e., negative, positive), three genes were found to be significantly associated with OS in univariate analyses (Table 6): BRCA1 (HR = 1.64, 95% CI = 1.12-2.39), TS (HR = 1.78, 95% CI = 1.24-2.56), and RRM2 (HR = 1.69, 95% CI = 1.17-2.44). (nih.gov)
  • The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. (cancerindex.org)
  • KDM5B favours breast cancer cell proliferation by repressing tumour suppressor genes BRCA1 and HOXA5. (thefreedictionary.com)
  • If BRG1 is defective, BRCA1 is no longer able to switch on transcription of p53-responsive genes. (sciencemag.org)
  • Dominant-negative HLH proteins encoded by Id-related genes, such as Id4, also contain the HLH-dimerization domain but lack the DNA-binding basic domain. (springer.com)
  • ATM promotes the activation of BRCA1, CHK2, and p53 leading to the induction of response genes such as CDKN1A (p21), GADD45A , and RRM2B that promote cell-cycle arrest and DNA repair. (aacrjournals.org)
  • DNA damage signaling is then propagated by ATM through activation of BRCA1, CHK2, and p53, leading to the induction of response genes involved in growth arrest, DNA repair, and/or apoptosis ( 1-3 ). (aacrjournals.org)
  • In this way, the researchers concluded that BRCA1 interacts physically with the progesterone receptor, and stops it from activating other genes. (innovations-report.com)
  • The BRCA genes encode proteins involved in error-free repair of DNA double-strand breaks. (aacrjournals.org)
  • Investigators from The Cancer Institute of New Jersey (CINJ) and a number of major cancer centers in Europe have identified the role a key protein plays in helping cells with mutant BRCA1 genes to survive. (healthcanal.com)
  • We have recently demonstrated that the transcriptional co-repressor C-terminal binding protein 2 (CtBP2) is overexpressed in epithelial ovarian carcinoma. (edu.au)
  • Immunohistochemical analysis of CtBP2 and BRCA1 staining of ovarian tissues was performed. (edu.au)
  • Immunohistochemistry illustrated a significant inverse CtBP2 and BRCA1 expression in a panel of malignant ovarian tumor tissues. (edu.au)
  • Conclusion CtBP2 is an ovarian cancer oncogene that may play a significant role in epigenetically silencing BRCA1 function in sporadic epithelial ovarian cancer. (edu.au)
  • Defects in BRCA1 are a cause of susceptibility to familial breast-ovarian cancer type 1 (BROVCA1), a condition associated with familial predisposition to cancer of the breast and ovaries, and pancreatic cancer type 4 (PNCA4). (activemotif.jp)
  • The breast and ovarian cancer type 1 susceptibility protein (BRCA1) has pivotal roles in the maintenance of genome stability. (nih.gov)
  • A model for targeting the breast and ovarian cancer type 1 susceptibility protein (BRCA1) to damage-induced foci at DNA double-stranded breaks that involves a ubiquitin-dependent signal transduction pathway. (nih.gov)
  • It is well known, along with BRCA 2, to cause hereditary breast and ovarian cancer, but here we will specifically focus on BRCA1. (springer.com)
  • Breast and ovarian cancer are associated with a breakdown in the repair systems involving these proteins. (innovations-report.com)
  • Eighty percent of women who inherit mutant forms of the BRCA1 protein develop breast cancer and 65% develop ovarian cancer. (mit.edu)
  • The FDA approval of the PARP inhibitor olaparib for fourth-line therapy of germline BRCA1/2-mutated ovarian cancer represents the first registered indication for this class of drugs in any disease. (aacrjournals.org)
  • Included in the 60-patient study were 19 BRCA1/2 -deficient patients with breast, ovarian, or prostate cancer, for whom the observed objective response rate (ORR) was 47% and the disease control rate was 63% ( 3 ). (aacrjournals.org)
  • BRCA1 is an E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. (activemotif.jp)
  • The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. (activemotif.jp)
  • Ubiquitin-binding protein (PubMed:24627472). (rcsb.org)
  • Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.37). (rcsb.org)
  • The BRCA1 -A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. (rcsb.org)
  • Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. (rcsb.org)
  • Does not bind Lys-48'-linked ubiquitin. (rcsb.org)
  • BRCA1-associated protein-1 (BAP1) is a component of the ubiquitin proteasome system (UPS) that has been implicated in lung and breast cancers ( 3 ). (aacrjournals.org)
  • In this system, ubiquitin is covalently conjugated to target proteins ( 7 ). (aacrjournals.org)
  • The attachment of ubiquitin to a substrate molecule can act as a targeting signal by delivering the modified protein to different locations in the cell or modifying its activity, macromolecular interactions, or half-life ( 8 ). (aacrjournals.org)
  • Because the full-length human BRCA1 is a ubiquitin ligase, it was hypothesized that autoubiquitinated BRCA1 might be a substrate for BAP1 deubiquitinating activity ( 3 ). (aacrjournals.org)
  • The IlE26Ala mutation abrogates the BRCA1 E3 ubiquitin ligase activity and is predicted to maintain the RING structure. (nih.gov)
  • Several functional assays have been conducted to evaluate VUS in BRCA1 at the level of its global and domain-based functions, including ubiquitin ligase activity assays, protease sensitivity assays, phosphopeptide binding assays, small colony phenotype assays, yeast localization phenotype assays, and embryonic stem cell-based functional assays (review in Millot et al. (plos.org)
  • Like other proteins, formation of K48-linked ubiquitin chains on histones targets them for proteasome mediated degradation. (frontiersin.org)
  • The mono-ubiquitylated FANCI-FANCD2 (ID) complex might promote the recognition and subsequent removal of DNA lesions through nucleolytic cleavage of DNA strands by recruitment of ubiquitin-binding proteins that are important for this repair process ( 11 - 16 ). (sciencemag.org)
  • DNA damage-response and -repair proteins can be recruited to sites of DNA damage via their ubiquitin-binding domains ( 17 - 20 ). (sciencemag.org)
  • Here we use massively parallel assays to measure the effects of nearly 2000 missense substitutions in the RING domain of BRCA1 on its E3 ubiquitin ligase activity and its binding to the BARD1 RING domain. (genetics.org)
  • Hashizume R, Fukuda M, Maeda I et al (2001) The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. (springer.com)
  • Kim H, Chen J, Yu X (2007) Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. (springer.com)
  • BARD1 forms a stable heterodimer with BRCA1, stimulating its nuclear localization and ubiquitin E3 ligase activity. (hindawi.com)
  • The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. (jax.org)
  • The only known enzymatic function of the BRCA1 tumor suppressor is the ubiquitin E3 ligase activity mediated by its N-terminal RING domain. (pubmedcentralcanada.ca)
  • Interestingly, the UBXN1 protein uses a ubiquitin-associated domain to interact preferentially with autoubiquitinated forms of BRCA1, providing a potential mechanism for spatial and/or temporal control of BRCA1 enzymatic function. (pubmedcentralcanada.ca)
  • In the BRCA1-A complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. (mybiosource.com)
  • Also known as BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1). (mybiosource.com)
  • RAP80: Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. (mybiosource.com)
  • [14] When the BRCA1/BARD1 heterodimer is transported to the damaged DNA site, it acts as an E3 ubiquitin ligase . (wikipedia.org)
  • Ubiquitination requires the E1 ubiquitin activating enzyme, an E2 ubiquitin conjugating enzyme, and frequently a substrate-specific ubiquitin protein ligase (E3). (asm.org)
  • One class of E3 ubiquitin ligases has been shown to contain a common zinc-binding RING finger motif. (asm.org)
  • We have previously shown that herpes simplex virus type 1 ICP0, itself a RING finger protein, induces the proteasome-dependent degradation of several cellular proteins and induces the accumulation of colocalizing conjugated ubiquitin in vivo. (asm.org)
  • We conclude that ICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and to target specific cellular proteins for destruction by the 26S proteasome. (asm.org)
  • It has been shown that ICP0 induces the proteasome-dependent degradation of two major components of ND10, PML itself and Sp100, particularly their isoforms that are covalently modified by the ubiquitin-like protein SUMO-1 ( 1 , 8 , 31 , 33 ). (asm.org)
  • In the BRCA1 -A complex, interacts directly with ABRAXAS1 . (rcsb.org)
  • [16] The BRCA1 protein associates with RNA polymerase II , and through the C-terminal domain, also interacts with histone deacetylase complexes. (wikipedia.org)
  • This RING domain interacts with associated proteins, including BARD1 , which also contains a RING motif, to form a heterodimer. (wikipedia.org)
  • Another corepressor is CtBP, which was discovered by the Chinnadurai group as a protein that interacts with the PLDLS sequence located in the C-terminal region of the E1A protein from adenovirus types 2 and 5 ( 8 , 9 ). (pnas.org)
  • Interacts with BRCA1 and ATM. (genecards.org)
  • We have now observed that PARP1 interacts with and poly-ADP-ribosylates (aka PARsylates) BRCA1. (aacrjournals.org)
  • In ER-α-positive MCF-7 cells and ER-α-negative Hela cells expressing exogenous ER-α, mutation of the Sp-binding site interfered with basal and estrogen-induced BRCA1 transcription. (biomedcentral.com)
  • Conversely, mutation of the CRE-binding element reduced basal BRCA1 promoter activity but did not prevent estrogen activation. (biomedcentral.com)
  • The three sites have an additive effect, and mutation of all three sites is necessary to abolish both binding to CtBP and repressor activity. (pnas.org)
  • Thompson D, Easton D, Breast Cancer Linkage Consortium (2002) Variation in BRCA1 cancer risks by mutation position. (springer.com)
  • By contrast, the mutation R1699L, which disrupts the binding of phosphorylated proteins (but which is not destabilizing), was completely inactive. (sigmaaldrich.com)
  • We have characterized a dissociation of function mutation of BRCA1 that preserves cell-cycle checkpoint function, but is highly defective in homologous recombination. (mskcc.org)
  • The removal of BRCA1 from the cells, which simulated what could happen in the cells of a person with a BRCA1 mutation, resulted in increased lipid storage, decreased insulin signaling, reduced mitochondrial function and increased oxidative stress. (eurekalert.org)
  • The mutation affects the ability of the Abraxas protein to enter the nucleus and bind to sites adjacent to damaged DNA. (healthcanal.com)
  • In addition, the researchers showed that the mutation impairs guiding of the Abraxas protein in cultured cells-the mutant protein in these cultures was also not recruited to sites of DNA damage compared to control cells in culture. (healthcanal.com)
  • What's more, expression of the Abraxas mutation caused hypersensitivity to ionizing radiation - a cause of DNA damage - and reduced BRCA1 localization at sites of DNA damage in several cell lines. (healthcanal.com)
  • Less known is information on other molecular events that may impact cancer formation in cells having a BRCA1 mutation. (healthcanal.com)
  • hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. (ebi.ac.uk)
  • The current hypothesis is that DNA damage ( 1 ) first triggers the ataxia telangiectasia mutated (ATM)-ataxia telangiectasia and RAD3-related protein (ATR)-dependent phosphorylation of histone variant H2AX ( 2 ). (nih.gov)
  • The unique aspect of our approach to this problem has been making the claim that phosphorylation of substrates by protein kinases alone may not be enough to elicit the particular molecular effects that are observed. (hstalks.com)
  • The CtIP/BRCA1 complex only exists in G 2 phase and is required for DNA damage-induced Chk1 phosphorylation and the G 2 /M transition checkpoint. (asm.org)
  • To obtain a systems-level overview of host signaling during infection, we analyzed the global dynamics of protein phosphorylation by liquid chromatography-tandem MS and identified several hundred of proteins undergoing a phosphorylation change during the first hours of infection. (mcponline.org)
  • Fuzzy c-means clustering identified six temporal profiles of phosphorylation and a functional module composed of ATM-phosphorylated proteins related to genotoxic stress. (mcponline.org)
  • Finally, we showed that S. flexneri effector OspF affected the phosphorylation of several hundred proteins, thereby demonstrating the wide-reaching impact of a single bacterial effector on the host signaling network. (mcponline.org)
  • CK2 is also involved in the phosphorylation of several proteins related to apoptosis, including apoptosis repressor with caspase recruitment domain ( 18 , 19 ), p53 ( 20 ), nuclear factor-κB ( 21 ), inhibitor of κB ( 22 ), as well as c-Myc ( 23 ). (aacrjournals.org)
  • Yu X, Fu S, Lai M et al (2006) BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP. (springer.com)
  • DSBs trigger a multitude of post-translational modifications that alter both, catalytic activities and the specificity of protein interactions including: phosphorylation, methylation, ubiquitylation, acetylation, and SUMOylation, followed by the turnaround of these changes as repair has been completed. (wikipathways.org)
  • Regulation of Mammalian STE20-like Kinase 2 (MST2) by Protein Phosphorylation/dephosphorylation and Proteolysis The Journal of Biological Chemistry. (jove.com)
  • A few studies have also implicated protein phosphorylation reactions in MST2 regulation. (jove.com)
  • In this study, we examined the mechanism of MST2 regulation with an emphasis on the relationship between caspase-3 cleavage and protein phosphorylation. (jove.com)
  • Sequencing of several cofilin gel spots revealed phosphorylation of serine 3, a post-translational modification associated with decreased actin binding and cytoskeletal reorganization. (mcponline.org)
  • Rb is a multifunctional protein with many binding and phosphorylation sites. (wikipedia.org)
  • Within each subunit, there are a variety of protein binding sites, as well as a total of 15 possible phosphorylation sites. (wikipedia.org)
  • Generally, phosphorylation causes interdomain locking, which changes Rb's conformation and prevents binding to target proteins. (wikipedia.org)
  • These enzymes are the largest single enzyme family in the human genome, and it is thought that at least 30% of all proteins are modified by phosphorylation. (mit.edu)
  • These modifications play a particularly significant role controlling the cell cycle and the response of cells of DNA damage, primarily by phosphorylation-dependent formation of multi-protein signaling complexes. (mit.edu)
  • The key function of the FA pathway is to orchestrate proteins involved in the repair of interstrand cross-links (ICLs), to prevent genomic instability and replication stress. (mdpi.com)
  • We report here that BRCA1 deficiency activates the AKT oncogenic pathway, one of the most common alterations associated with human malignancy. (aacrjournals.org)
  • Our results show that BRCA1 is a negative regulator of the AKT pathway and imply the significance of the BRCA1/AKT pathway in tumorigenesis. (aacrjournals.org)
  • Both AKT and BRCA1 regulate the cell cycle and genomic stability through the CHK1 pathway ( 2 , 13 ), and BRCA1 regulates estrogen receptor-α activity in a phosphoinositide 3-kinase/AKT-dependent manner ( 14 ), strongly supporting the notion that the AKT pathway contributes to BRCA1-mediated tumorigenesis. (aacrjournals.org)
  • A central event in the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex. (sciencemag.org)
  • In addition, the large number of PML-associated proteins that do not appear to act in a single pathway suggests that PML-NBs could be depots for storage and titration of nuclear proteins ( Seeler and Dejean, 1999 ). (biologists.org)
  • Also, other proteins which involved in the same pathway with BRCC3 were listed below. (creativebiomart.net)
  • BRCA1 enters the nucleus through the importin-alpha/beta pathway and locates at nuclear DNA replication sites. (hindawi.com)
  • The mechanism of inactivating the BRCA pathway in sporadic cancers is under investigation, but appears to be upstream of BRCA1 in the majority of cases studied so far. (mskcc.org)
  • May also act as a death receptor-associated anti-apoptotic protein, which inhibits the mitochondrial apoptotic pathway. (mybiosource.com)
  • BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair. (nih.gov)
  • Thus, BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites. (nih.gov)
  • The TA assay shows that variants Y1703S, W1718L and G1770V dramatically compromise the transcriptional activity of BRCA1, while variants Q1409L, S1473P, E1586G and R1589H behave like wild-type BRCA1. (plos.org)
  • In the work presented here, we combine a functional assay - the transcription activation (TA) assay, which is based on the function of the BRCA1 carboxy-terminal region (aa 1396-1863) in transcriptional activation domain when linked to a sequence-specific DNA binding module - [10] with protein structural analyses [11] to assess the functional impact of seven BRCA1 C-terminal VUS. (plos.org)
  • BRCA1 has been implicated in DNA damage repair, cell cycle checkpoint control, transcriptional regulation, and maintenance of genomic stability, which are key factors in tumorigenesis ( 1 , 2 ). (aacrjournals.org)
  • Thus, this protein plays a role in transcription, and DNA repair of double-strand DNA breaks [14] ubiquitination , transcriptional regulation as well as other functions. (wikipedia.org)
  • The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. (abcam.com)
  • A number of transcriptional activators regulate transcription through interaction with a coactivator protein, the best studied of which is CBP/p300 ( 3 ). (pnas.org)
  • Recently, it was shown that transcriptional repression by snail depends on its binding to CtBP ( 10 ), and that CtBP is essential for mesoderm formation and patterning in early Drosophila embryos ( 26 ). (pnas.org)
  • Consequently, Id proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins (Lasorella et al. (springer.com)
  • This superfamily represents a ssDNA-binding transcriptional regulator domain consisting of a helix-swapped dimer of beta(4)-alpha motifs. (ebi.ac.uk)
  • Members of this family of transcriptional regulators, which preferentially bind single-stranded DNA, include PBF-2 from plants, the mammalian nuclear factor 1-X (NF1-X), and positive cofactor 4 (PC4). (ebi.ac.uk)
  • NF1-X consists of two functionally distinct domains: a conserved N-terminal DNA-binding domain and a C-terminal transcriptional regulatory domain. (ebi.ac.uk)
  • Expression, DNA-binding specificity and transcriptional regulation of nuclear factor 1 family proteins from rat. (ebi.ac.uk)
  • The tumor suppressor p53 binding protein 1 (53BP1) binds to the DNA-binding domain of p53 and enhances p53-mediated transcriptional activation. (rupress.org)
  • The present review summarizes the current knowledge of SAFB1 and SAFB2 proteins in transcriptional repression with relevance to cancer. (biochemsoctrans.org)
  • BRCA1-associated protein-1 (BAP1), a deubiquitinating enzyme of unknown cellular function, is mutated in breast and lung cancers. (aacrjournals.org)
  • Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers. (mdpi.com)
  • Because of this, Greenberg says, there are some possible applications for making PARP chemotherapy more sensitive: "If you could inhibit specific acetylation events, then a patient's response to PARP inhibitors might be enhanced by hyperactivating 53BP1 binding to breaks in the context of BRCA1 deficient cancers. (innovations-report.com)
  • Typically, Id proteins are highly expressed during embryogenesis and expressed at lower levels in mature tissues, with the exception of some stem cells and many cancers (reviewed in Lasorella et al. (springer.com)
  • Moreover loss of normal production of the 53BP1 protein was found in a subset of BRCA1 -associated cancers and in sporadic "triple-negative" breast cancers in two independent breast cancer patient cohorts from the United States and Finland. (healthcanal.com)
  • According to the investigators, these data suggest that loss of 53BP1 may allow cells to tolerate loss of BRCA1 , and that some breast cancers may have acquired loss of 53BP1 protein expression. (healthcanal.com)
  • BRCA1 combines with other tumor suppressors, DNA damage sensors and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). (wikipedia.org)
  • excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). (nih.gov)
  • In contrast, proteins suppressed in FH lines include the 27-kDa heat shock protein, translationally controlled tumor protein, and several proteins associated with actin modification such as actin prepeptide, F-actin capping protein α subunit, and cofilin. (mcponline.org)
  • Also known as BRCA1-A complex subunit Abraxas (Coiled-coil domain-containing protein 98) (Protein FAM175A). (mybiosource.com)
  • These effects appear to be related to the unique 3-subunit structure, where two of the subunits or rings are involved in binding to the minor groove of DNA in guanine-cytosine rich sequences and alkylation N2 of guanine forming adducts that distorted the DNA helix structure and they are recognized by the TC-NER mechanism. (knowcancer.com)
  • We have also detected other substrates for ICP0-induced degradation, including the catalytic subunit of DNA protein kinase ( 35 ) and the centromere proteins CENP-C ( 7 ) and CENP-A ( 27 ). (asm.org)
  • Plays a central role in the BRCA1 -A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1 - BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). (rcsb.org)
  • Component of the BRCA1 -A complex, at least composed of the BRCA1 , BARD1 , UIMC1 /RAP80, ABRAXAS1 , BRCC3 / BRCC3 6, BABAM2 and BABAM1 /NBA1. (rcsb.org)
  • It was later shown, however, that BAP1 does not seem to function in the deubiquitination of the BRCA1/BARD1 complex ( 10 ). (aacrjournals.org)
  • Localization of BRCA1 is regulated by interactions with other proteins such as the BRCA1-associated RING domain protein 1 (BARD1) [ 19 , 20 ]. (mdpi.com)
  • BRCA1 exists as a stable heterodimer through its RING-mediated interaction with BRCA1-associated RING domain protein 1 (BARD1), which is inhibited by BRCA1-associated protein 1 (BAP1). (nih.gov)
  • B-F) Scoring the E3 ligase and BARD1-binding activities of BRCA1 RING domain variants. (genetics.org)
  • The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. (cancerindex.org)
  • Brzovic PS, Rajagopal P, Hoyt DW et al (2001) Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. (springer.com)
  • BRCA1 is a multifunctional protein that binds dozens of other proteins, the most important of which is BARD1 [ 9 - 11 ] (see Figure 1(a) ). (hindawi.com)
  • a) Protein domain structure of BRCA1 showing the location of nuclear localization signals (NLSs), nuclear export signals (NESs), and binding sites for BARD1 and gamma-tubulin. (hindawi.com)
  • Once translated in the cytoplasm, BRCA1 can move to the centrosome where it dimerizes with BARD1 to ubiquitinate proteins such as gamma-tubulin that regulate centrosome duplication and microtubule nucleation, or to the mitochondria where it is implicated in cell survival and/or apoptosis regulation. (hindawi.com)
  • In response to DNA damage, BRCA1 is sequestered (as a dimer with BARD1) to different types of DNA repair complexes at foci. (hindawi.com)
  • The interaction with BARD1 tends to trap BRCA1 in the nucleus through the masking of its NES. (hindawi.com)
  • If BRCA1 is not bound to BARD1, it is exported to the cytoplasm by the CRM1 export receptor, and this has been linked to the roles of BRCA1 in apoptosis and in centrosome duplication as revealed by functional comparison of wild-type and NES-mutated forms of BRCA1. (hindawi.com)
  • Immunocytochemical staining and in vitro binding assay revealed that UBE2T interacted and colocalized with the BRCA1/BRCA1-associated RING domain protein (BARD1) complex. (aacrjournals.org)
  • Our data imply a critical role of UBE2T in development and/or progression of breast cancer through the interaction with and the regulation of the BRCA1/BARD1 complex. (aacrjournals.org)
  • The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. (mybiosource.com)
  • Most, if not all, BRCA1 heterodimerizes with BARD1 in vivo . (wikipedia.org)
  • [9] BARD1 and BRCA1 form a heterodimer via their N-terminal RING finger domains . (wikipedia.org)
  • The BARD1-BRCA1 interaction is observed in vivo and in vitro and is essential for BRCA1 stability. (wikipedia.org)
  • The BARD1 protein also contains three tandem ankyrin repeats . (wikipedia.org)
  • [8] BARD1 expression is upregulated by genotoxic stress and involved in apoptosis through binding and stabilizing p53 independently of BRCA1. (wikipedia.org)
  • BARD1 is vital in the rapid relocation of BRCA1 to DNA damage sites. (wikipedia.org)
  • [13] Double stranded breaks (DSB) in DNA trigger poly(ADPribose) polymerase 1 (PARP1) to catalyze the formation of poly(ADPribose) (PAR) so that PAR can then bind to an array of DNA response proteins, including the BRCA1/BARD1 heterodimer, and target them to DNA damage sites. (wikipedia.org)
  • [9] The BRCA1/BARD1 heterodimer ubiquitinates RNA polymerase II, preventing the transcription of the damaged DNA, and restoring genetic stability. (wikipedia.org)
  • Inhibiting cancer cells' BRCA1/BARD1 heterodimer from relocating to DNA damage sites would induce tumor cell death rather than repair. (wikipedia.org)
  • Inhibiting this lysine residue's ability to bind poly(ADP-ribose) would prevent the BRCA1/BARD1 heterodimer from localizing to DNA damage sites and subsequently prevent DNA damage repair. (wikipedia.org)
  • We also show that this interaction is disrupted by single nucleotide substitutions in the BRCA1 3'UTR and that endogenous HuR protein associates with BRCA1 transcripts in T47D and MCF7 breast cancer cells. (edu.au)
  • Recombinant BRCA1 is suitable for in vitro function studies including transcription and DNA repair, for protein-protein interaction assays and cell growth assays. (activemotif.jp)
  • 50 ng is sufficient for reconstituted transcription assays and 100 ng is sufficient for protein-protein interaction studies. (activemotif.jp)
  • Using transfection studies with wild-type and mutated BRCA1 promoter constructs, electromobility binding and shift assays, and DNA-protein interaction and chromatin immunoprecipitation assays, we investigated the role of Sp-binding sites and cAMP response element (CRE)-binding sites harbored in the proximal BRCA1 promoter. (biomedcentral.com)
  • Critically, two point mutants (L21P and L24P) of the PALB2 coiled-coil domain or an NH 2 -terminal deletion (Δ1-70) disrupt its interaction with BRCA1. (aacrjournals.org)
  • B) In vitro interaction assay using recombinant GST-BRCA1 fragments performed in HeLa cells. (nih.gov)
  • The CREB protein carries out its function by activating transcription, where interaction with transcription factors is managed by one or more CREB domains: the nuclear receptor interaction domain (RID), the KIX domain (CREB and MYB interaction domain), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). (wikipedia.org)
  • As the DNA bends, its contact with TBP increases, thus enhancing the DNA-protein interaction. (wikipedia.org)
  • Instead, it appears to be the interaction of the phosphorylated substrates with specific phosphoserine, phosphothreonine or phosphotyrosine-binding domains that coordinates the action of the protein kinase with the molecular effect that we observe. (hstalks.com)
  • In spite of extensive efforts studying BRCA1 and AKT individually, an interaction of BRCA1 and AKT has not been reported. (aacrjournals.org)
  • Moreover, the interaction between CtIP and BRCA1, although dispensable for resection of endonuclease-generated DSB ends, is required for resection of Top2-adducted DSBs, as well as for cellular resistance to etoposide during genomic DNA replication. (rupress.org)
  • The BRCA1 tumor suppressor is a 1863 amino acid protein with multiple protein interaction domains that facilitate its roles in regulating DNA repair and maintenance, cell cycle progression, transcription, and cell survival/apoptosis. (hindawi.com)
  • Indeed, RNA-protein interaction and siRNA experiments showed that the skipping of T6 BRCA1 exon 18 is due to the creation of a splicing factor-dependent silencer. (asm.org)
  • Despite recent large-scale protein-protein interaction profiling efforts, DYRK1A interactions specific to different subcellular compartments remain largely unknown, impeding progress toward understanding emerging roles for this kinase. (nature.com)
  • this favors protein-protein interactions by presenting a larger interaction surface allowing multiple binding partners. (springer.com)
  • p. 2787-2798 ) show that the UBXN1 protein binds the RING domain of BRCA1 and inhibits its E3 ligase activity. (pubmedcentralcanada.ca)
  • Finally, we report that the MEK1 (mitogen-activated protein kinase kinase-1) inhibitor PD98059 attenuated the recruitment of Sp1 and phosphorylated ER-α, respectively, to the Sp and AP-1 binding element. (biomedcentral.com)
  • It's well established that in response to various types of stimuli, such as growth factor stimulation or DNA damage, protein kinase has become activated in cells and phosphorylate, a subset of proteins within the cell and these phosphorylated substrates then are believed to be responsible for many of the molecular effects that follow after the initial stimulus. (hstalks.com)
  • They also provide access to DDR sensors such as the Mre11-Rad50-Nbs1 (MRN) complex which binds double strand breaks (DSBs) and recruits ATM kinase (Figure 1 ) and the replication protein A (RPA) complex which responds predominantly to single strand DNA lesions and recruits ATR kinase. (frontiersin.org)
  • Protein kinase CK2 is implicated in cellular proliferation and transformation. (aacrjournals.org)
  • An induced overexpression of CK2α increased the levels of Ser 473 phosphorylated (p)-Akt/protein kinase B (PKB), p-PDK1, pFKHR, p-BAD, Bcl-2, Bcl-xL, Mcl-1, and XIAP. (aacrjournals.org)
  • These findings strongly suggest protein kinase CK2α as an unfavorable prognostic marker and novel therapeutic target in AML. (aacrjournals.org)
  • Protein kinase CK2 (formerly casein kinase II) is a highly conserved and ubiquitously expressed serine/threonine kinase ( 1 - 3 ) with a tetrameric structure consisting of two catalytic (α or α′ or both) and two regulatory β subunits ( 2 , 4 , 5 ). (aacrjournals.org)
  • CK2 is a remarkably multifunctional protein kinase with a vast array of more than 300 substrates, many of which are critically involved in the process of cell growth, proliferation, and differentiation ( 7 - 14 ). (aacrjournals.org)
  • Increasing evidence indicates that CK2 enzyme is a component of regulatory protein kinase networks that are involved in several aspects of cellular transformation and cancer ( 13 , 26 - 30 ). (aacrjournals.org)
  • The chromosome 21 encoded protein kinase DYRK1A is essential for normal human development. (nature.com)
  • A major role is that of the MRN (MRE11/RAD50/NBS1) complex binding to DSBs and facilitating the activation of ATM (Ataxia Telangiectasia Mutated) protein, a key PI3K (Phosphatidylinositol 3-kinase) related kinase in the DNA damage response (DDR). (wikipathways.org)
  • Located on chromosome 11q 22-23, it includes 66 exons with a 9168 base pair coding sequence, and encodes a PI3K-related serine/threonine protein kinase (PIKK) that helps maintain genomic integrity. (aacrjournals.org)
  • Our proteomic approach utilizes libraries of phosphorylated peptides that mimic the sequence produced by a protein kinase. (mit.edu)
  • BRCA1 PARsylation is a key event in this process, failure of which triggers hyper-recombination and chromosome instability. (aacrjournals.org)
  • In vertebrate cells, the elimination of DSBs with minimal nucleotide sequence change involves the spatiotemporal orchestration of an apparently endless number of proteins ranging, according to their action, from the nucleotide level to nucleosome organization and chromosome architecture. (wikipathways.org)
  • IMP) is mainly cytoplasmic and binds to the NLS motifs of BRCA1 with similar specificity to that of importin alpha. (abcam.com)
  • This protein also contains nuclear localization signal s and nuclear export signal motifs. (wikipedia.org)
  • BRCA1-binding motifs are S..F.K (high affinity) or S..F (lower affinity) ( Clapperton,2004 ). (eu.org)
  • Metazoa MDC1 binds histone H2AX C-terminal S..Y$ motifs ( Lee,2005 ), which may be S..F$ in plants and S..L$ in Fungi , but experimental evidence has been lacking. (eu.org)
  • These proteins are structurally similar, consisting of a helix-swapped dimer of beta(4)-alpha motifs. (ebi.ac.uk)
  • Kinases, the primary enzyme involved in signal transduction, modify proteins by recognizing particular linear sequence motifs in proteins, and covalently modifying them by attaching a phosphate group to serine, threonine, or tyrosine residues within the protein. (mit.edu)
  • Our lab uses oriented peptide library technology to identify the motifs that are recognized and phosphorylated by protein kinases involved in cell cycle control. (mit.edu)
  • Many of these motifs are conserved in proteins from yeast to humans. (mit.edu)
  • The purpose of the study was to analyze the contribution of cis -acting sites flanking the AP-1 element to basal and estrogen-dependent regulation of BRCA1 transcription. (biomedcentral.com)
  • These cumulative findings suggest that the proximal BRCA1 promoter segment comprises cis -acting elements that are targeted by Sp-binding and CRE-binding proteins that contribute to regulation of BRCA1 transcription. (biomedcentral.com)
  • In this review, we present an overview of both canonical (regulation of interstrand cross-links repair, ICLs) and noncanonical roles of FA proteins. (mdpi.com)
  • Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. (mdpi.com)
  • In this review, we briefly summarize BRCA1's many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. (mdpi.com)
  • However, several lines of evidence suggest a role for BRCA1 in the regulation of AKT. (aacrjournals.org)
  • This paper will focus on the transport, dynamics, and multiple intracellular destinations of BRCA1 with emphasis on how regulation of these events has impact on, and determines, a broad range of important cellular functions. (hindawi.com)
  • The primary tumor suppressing role of BRCA1 relates to the maintenance of genomic integrity through regulation of DNA replication, repair, and transcription, in addition to various cell cycle checkpoints that ensure survival of healthy cells [ 6 ]. (hindawi.com)
  • We are characterizing the relationship of the BRCA1 superfamily in the regulation of homologous recombination. (mskcc.org)
  • 13, 266-267] has emphasized the potential importance of the BRCA1 C-terminal region for BRCA1-mediated breast cancer suppression, as this domain shows similarities with the C-terminal regions of a p53-binding protein (53BP1), the yeast RAD9 protein involved in DNA repair, and two uncharacterized, hypothetical proteins (KIAA0170 and SPAC19G10.7). (nih.gov)
  • Roger A. Greenberg, M.D., Ph.D., associate investigator, Abramson Family Cancer Research Institute and associate professor of Cancer Biology at the Perelman School of Medicine, University of Pennsylvania, together with postdoctoral researcher Jiangbo Tang Ph.D. and colleagues, found a key determinant in the balance between two proteins, BRCA1 and 53BP1, in the DNA repair machinery. (innovations-report.com)
  • The two proteins, BRCA1 and 53BP1, control which of two cell-repair mechanisms will be used: homologous recombination or non-homologous end-joining, technically speaking. (innovations-report.com)
  • If H4 is acetylated at a specific location, then 53BP1 binding near the broken DNA region is strongly reduced. (innovations-report.com)
  • On the other hand, if acetylation is reduced, 53BP1 outcompetes BRCA1 at a break and the non-homologous end-joining tool repairs the break. (innovations-report.com)
  • Work from several other research teams surprisingly has shown that if neither BRCA nor 53BP1 are available, then the homologous recombination system goes into action even in the absence of BRCA1 and BRCA1 mutant cancer cells become resistant to PARP inhibitors. (innovations-report.com)
  • However, we were able to show that 53BP1 doesn't bind well to regions of histone H4 that are acetylated at a specific location on H4. (innovations-report.com)
  • The MDC1 protein has been shown to help mediate Rad51 to the sites of DNA damage, whereas 53BP1 appears to prevent the processing of DNA double-strand breaks mediated by BRCA1 for homologous recombination. (mskcc.org)
  • It recruits and cooperates with other sensor proteins, including 53BP1 (p53-binding protein) and BRCA1 (breast cancer type 1). (aacrjournals.org)
  • Other proteins localize the signaling to the damage site, such as 53BP1, which recruits p53. (emdmillipore.com)
  • It was found that loss of another DNA repair protein, 53BP1 (p53 Binding Protein 1) allows cells to continue growing after loss of BRCA1 . (healthcanal.com)
  • ChIP and luciferase reporter assays using a BRCA1 promoter-regulated luciferase construct indicated that the CtBP2 complex binds the BRCA1 promoter and represses BRCA1 transcription. (edu.au)
  • BRCA1 associates with other tumor suppressors, DNA repair proteins, and signal transducers in a large complex known as the BRCA1-associated genome surveillance complex (BASC) that functions to identify double-strand DNA breaks and either repair them or destroy cells where DNA damage cannot be repaired. (activemotif.jp)
  • Gel mobility shift and competition assays identified a DNA-protein complex recognizing the CRE motif that we were able to supershift using CREB-specific antibody. (nih.gov)
  • We previously reported that estrogen stimulated BRCA1 transcription through the recruitment of a p300/ER-α complex to an AP-1 site harbored in the proximal BRCA1 promoter. (biomedcentral.com)
  • TFIID is the first protein to bind to DNA during the formation of the transcription preinitiation complex of RNA polymerase II (RNA Pol II). (wikipedia.org)
  • This region modulates the DNA binding activity of the C-terminus, and modulation of DNA-binding affects the rate of transcription complex formation and initiation of transcription. (wikipedia.org)
  • The MRN complex also has other functions not related to its role in the BRCA1 C complex. (genenames.org)
  • The complex formation of BRCA1-RBBP8-MRN is important for facilitating DSB resection to generate single-stranded DNA that is needed for HR-mediated DSB repair. (genenames.org)
  • In response to DNA damage, ATM is autophosphorylated within a MRN multiprotein complex that binds DSBs. (frontiersin.org)
  • However, the CtIP/BRCA1 complex is not required for the damage-induced G 2 accumulation checkpoint, which is controlled by a separate BRCA1/BACH1 complex. (asm.org)
  • Upon contact between the tip complex of the type III apparatus and host cell receptors, including α5β1-integrins and CD44, the secreted proteins IpaB and IpaC insert into the plasma membrane and form a pore into the host membrane through which several effectors translocate ( 10 ⇓ ⇓ ⇓ - 14 ). (mcponline.org)
  • Thus, the mono-ubiquitylated ID complex recruits the downstream repair protein FAN1 and facilitates the repair of DNA interstrand cross-links. (sciencemag.org)
  • We repeatedly found the ID complex as major FAN1-associated proteins (fig. S2A). (sciencemag.org)
  • Mass spectrometry analyses of triple-tagged FANCD2-associated protein complexes revealed peptides that corresponded to FAN1 (fig. S2B), indicating that these proteins probably form a complex in vivo. (sciencemag.org)
  • Examples of such corepressors are the sin3/NCoR/histone deacetylase complex, retinoblastoma protein/histone deacetylase complex, and Groucho and Nab proteins ( 4 - 7 ). (pnas.org)
  • Through biochemical analysis in Xenopus laevis egg extracts, we establish that the MRN (Mre11, Rad50, and Nbs1) complex, CtIP, and BRCA1 are required for both the removal of Top2-DNA adducts and the subsequent resection of Top2-adducted DSB ends. (rupress.org)
  • The Mre11 complex, composed of the proteins MRE11, NBS1, and RAD50, is a vital component in the DNA damage response and is at least partially responsible for connecting DNA damage detection to DNA repair and cell cycle checkpoint functions. (bmj.com)
  • 21 Both of these highly conserved domains are involved in protein-protein interactions and are therefore crucial for the functions of the Mre11 complex, including its subcellular localisation after DNA damage. (bmj.com)
  • ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). (genecards.org)
  • Structural basis for cell cycle checkpoint control by the BRCA1-CtIP complex. (eu.org)
  • Wang B, Matsuoka S, Ballif BA et al (2007) Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. (springer.com)
  • This complex plays a role in the DNA damage response, where it is responsible for the stable accumulation of BRCA1 at DNA break sites. (creativebiomart.net)
  • We previously found that BRCA1 HRR function is regulated by the RAP80 complex, but the mechanism was unclear. (aacrjournals.org)
  • Within the SWI/SNF complex, BRCA1 binds to a DNA-dependent ATPase called BRG1, the catalytic component that is essential for chromatin remodeling. (sciencemag.org)
  • the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. (nih.gov)
  • Once they established that the two proteins complex together, they sought to answer if BRCA1 plays a critical role in regulating muscle metabolic function. (eurekalert.org)
  • Abraxas organizes a large BRCA1 protein-containing complex that is required to fix DNA-damage. (healthcanal.com)
  • Moreover, UBE2T protein was shown to bind FANCL, the Fanconi anaemia core complex, and to be necessary for the efficient DNA damage-induced monoubiquitination of FANCD2, one of Fanconi anaemia core complex subunits ( 13 , 14 ). (aacrjournals.org)
  • Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. (mybiosource.com)
  • Below are the list of possible BRCA1-A complex products. (mybiosource.com)
  • Taken together, these data not only implicate CtIP as a critical player in cell cycle checkpoint control but also provide molecular mechanisms by which BRCA1 controls multiple cell cycle transitions after DNA damage. (asm.org)
  • CtBP recently has been shown to bind to another mammalian protein, CtIP ( 11 ). (pnas.org)
  • The Cambridge team's latest results suggest that a protein called CtIP is the master switch that flips the cell between the two pathways. (cancerresearchuk.org)
  • Ed Yong, Cancer Research UK's health information manager, revealed: "Our cells have two major ways of repairing broken DNA and this study shows that the CtIP protein is a switch that flicks between them. (cancerresearchuk.org)
  • The full-length BRCA1 cDNA encodes a large protein of 1863 amino acids ( Figure 1 ) [ 4 ]. (mdpi.com)
  • In particular, BRCA1 encodes for a protein of 1,863 amino acids and with multiple functional domains [8] . (plos.org)
  • When TBP binds to a TATA box within the DNA, it distorts the DNA by inserting amino acid side-chains between base pairs, partially unwinding the helix, and doubly kinking it. (wikipedia.org)
  • TBP binds with the negatively charged phosphates in the DNA backbone through positively charged lysine and arginine amino acid residues. (wikipedia.org)
  • There are six known isoforms of BRCA1, [28] with isoforms 1 and 2 comprising 1863 amino acids each. (wikipedia.org)
  • The RING motif , a Zn finger found in eukaryotic peptides, is 40-60 amino acids long and consists of eight conserved metal-binding residues, two quartets of cysteine or histidine residues that coordinate two zinc atoms. (wikipedia.org)
  • These proteins contain an HLH domain, which mediates homo- and heterodimerization, plus an adjacent DNA-binding region rich in basic amino acids. (springer.com)
  • 1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2. (patentdocs.org)
  • BRCA1 also associates with RNA pol II and histone deacetylase complexes to modulate transcription. (activemotif.jp)
  • The Sp factors have been shown to bind directly to the consensus GC-rich region 5'-(G/T)GGGCGG(G/A)(G/A)-3' or DNA-bound AP-1 transcription complexes [ 8 ]. (biomedcentral.com)
  • In addition, recent proteomic and genetic studies have revealed the presence of distinct BRCA1 complexes in vivo, each of which governs a specific cellular response to DNA damage. (nih.gov)
  • Moreover, RAP80 contains a poly-ADP-ribose-interacting domain that binds PARsylated BRCA1 and helps to maintain the stability of PARP1-BRCA1-RAP80 complexes. (aacrjournals.org)
  • By binding to specific phosphorylated sequences on proteins, these binding domains orchestrate the formation of signaling complexes that, in turn, control the cell cycle. (mit.edu)
  • Active Motif » Recombinant BRCA1 for in vitro transcription and DNA repair analysis, and protein-binding and cell growth assays. (activemotif.jp)
  • Our objectives were to characterize the functional effects of DNA methylation in the BRCA1 promoter and to clarify the functional status of the BRCA1 CRE (cAMP response element) motif. (nih.gov)
  • Furthermore this CRE is methylation sensitive, and we localized this methylation effect to a CpG dinucleotide within the BRCA1 CRE motif. (nih.gov)
  • We report that in the BRCA1 promoter the AP-1 site is flanked upstream by an element (5'-GGGGCGGAA-3') that recruits Sp1, Sp3, and Sp4 factors, and downstream by a half CRE-binding motif (5'-CGTAA-3') that binds CRE-binding protein. (biomedcentral.com)
  • [30] This motif contains a short anti-parallel beta-sheet , two zinc-binding loops and a central alpha helix in a small domain. (wikipedia.org)
  • The high affinity motif has an additional bound lysine residue (S..F.K). (eu.org)
  • Achsel T, Stark H, Luhrmann R (2001) The Sm domain is an ancient RNA-binding motif with oligo(U) specificity. (springer.com)
  • In combination with the AP-1/CRE sites, the Sp-binding domain enhanced the recruitment of nuclear proteins to the BRCA1 promoter. (biomedcentral.com)
  • In the presence of a TATA-less promoter, TBP binds with the help of TBP-associated factors (TAFs). (wikipedia.org)
  • CtBP does not bind directly to DNA but when tethered directly to the promoter through a Gal4 DNA binding domain CtBP efficiently represses transcription, demonstrating that the protein is a corepressor ( 10 ). (pnas.org)
  • [16] Rb binds and inhibits E2 promoter-binding-protein-dimerization partner (E2F-DP) dimers, which are transcription factors of the E2F family that push the cell into S phase. (wikipedia.org)
  • This protein acetylates both histone and non-histone proteins. (wikipedia.org)
  • This protein shares regions of very high sequence similarity with protein EP300 in its bromodomain, cysteine-histidine-rich regions, and histone acetyltransferase domain. (wikipedia.org)
  • BRAP2 may function as a cytoplasmic retention protein and play a role in regulating transport of nuclear proteins. (abcam.com)
  • The presence of PML (promyelocytic leukaemia) protein within this body suggests it to be a giant PML nuclear body (PML-NB). (biologists.org)
  • Indeed, in a large proportion of ICF cells at the G2 phase, HP1α, HP1β and HP1γ protein isoforms showed an aberrant signal concentrated into a large prominent nuclear body. (biologists.org)
  • We also demonstrated that the PML (promyelocytic leukaemia) protein, the major component of normal PML nuclear bodies (PML-NBs), accumulates at the aberrant HP1 body, identifying this structure as a giant PML-NB. (biologists.org)
  • They are found in nuclear proteins that are typically associated with cell cycle checkpoint functions responsive to DNA damage ( Glover,2004 ). (eu.org)
  • BRCA1 was first identified as a nuclear phosphoprotein, but has since been shown to contain different transport sequences including nuclear export and nuclear localization signals that enable it to shuttle between specific sites within the nucleus and cytoplasm, including DNA repair foci, centrosomes, and mitochondria. (hindawi.com)
  • During the infectious process, bacteria use a sophisticated delivery system, the type III secretion apparatus, to inject multiple effector proteins that subvert cellular and immune functions of macrophages and epithelial cells ( 2 ). (mcponline.org)
  • Our findings that chromatin-remodelling proteins fail to accumulate around satellite DNA in PML-deficient NB4 cells support a central role for PML protein in this cellular function. (biologists.org)
  • DYRK1A regulates a diverse array of cellular processes through physical interactions with substrates and binding partners in various subcellular compartments. (nature.com)
  • Proteasome-dependent degradation of ubiquitinated proteins plays a key role in many important cellular processes. (asm.org)
  • Since the proteasome inhibitor MG132 interferes with the ability of ICP0 to stimulate viral infection and reactivation from quiescence ( 14 ), it is likely that these effects on cellular proteins reflect a major biological function of ICP0. (asm.org)
  • SAFB1 (scaffold attachment factor B1) and a second family member SAFB2, are multifunctional proteins implicated in a variety of cellular processes including cell growth, apoptosis and stress response. (biochemsoctrans.org)
  • Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of transcription termination regions. (nih.gov)
  • The BRCA1 protein and its binding transcription factors. (mdpi.com)
  • The CREB protein domains, KIX, TAZ1 and TAZ2, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53. (wikipedia.org)
  • The aim of the present study is to functionally assess a set of 7 missense VUS (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L and G1770V) located in the C-terminal region of BRCA1 by combining in silico prediction tools and structural analysis with a transcription activation (TA) assay. (plos.org)
  • The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box. (wikipedia.org)
  • Each of these transcription factors contains several protein subunits. (wikipedia.org)
  • The TATA-box binding protein (TBP) is required for the initiation of transcription by RNA polymerases I, II and III, from promoters with or without a TATA box. (wikipedia.org)
  • The binding of these kinases to damaged DNA triggers the recruitment of additional proteins, many of which become phosphorylated and activated to further transduce signals that orchestrate DNA replication, cell cycle control, transcription, repair of damage, and/or survival versus death. (frontiersin.org)
  • This tract is consistent with similar tracts which are preferentially found in many transcription factors and generally act as a flexible spacer element located between the functional domains of a protein and therefore essential to protein conformation, protein-protein interactions, and/or DNA binding. (springer.com)
  • RB/E2F-family proteins repress transcription. (wikipedia.org)
  • NF1-X is one of several NF1 proteins that function as transcription factors. (ebi.ac.uk)
  • PC4 (or P15) possess the ability to co-activate and suppress transcription via its DNA-binding activity. (ebi.ac.uk)
  • A new family of plant transcription factors displays a novel ssDNA-binding surface. (ebi.ac.uk)
  • C-terminal domain of transcription cofactor PC4 reveals dimeric ssDNA binding site. (ebi.ac.uk)
  • This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins, and DNA repair pathways, resulting in perturbation of the cell cycle. (knowcancer.com)
  • The wild-type BRCA1 protein (1-1863 residues, accession number NM_007294) was expressed in a baculovirus system with an N-terminal His-Tag and purified by an affinity column in combination with FPLC chromatography. (activemotif.jp)
  • A phospho specific peptide corresponding to residues surrounding S1423 of human BRCA1. (abcam.com)
  • BRCA1 is composed of 215 residues. (bioquest.org)
  • RBPs regulate stability, maturation, and turnover of all RNAs, often binding thousands of targets at many sites. (springer.com)
  • To investigate the possibility that these two molecules are functionally linked in breast cancer, we performed bioinformatic analysis of the BRCA1 3' untranslated region (UTR), RNA-protein assays with the HuR protein and the BRCA1 3'UTR, and immunohistochemical analysis of a cohort of breast tumors using antibodies against BRCA1 and HuR. (edu.au)
  • Luciferase reporter assays confirm that an intact CRE is important for BRCA1 expression in transient transfections. (nih.gov)
  • A) Scheme for leveraging scores from parallelized assays for BRCA1 RING function into predictions for the function of the full-length BRCA1 protein in homology-directed DNA repair. (genetics.org)
  • Here, we show that an NH 2 -terminal coiled-coil domain of PALB2 is required for coimmunoprecipitation of PALB2 with BRCA1 and for the localization of PALB2. (aacrjournals.org)
  • However, the extent to which BRCA1-activated molecular pathways contribute to its tumor suppressor activity remains unclear. (aacrjournals.org)
  • BRCA1 domain structure and subcellular transport pathways. (hindawi.com)
  • binding domains from the cell, and map them onto signaling pathways in a system-wide manner. (mit.edu)
  • Interestingly, in vivo ubiquitination assay indicated BRCA1 to be polyubiquitinated by incubation with wild-type UBE2T protein, but not with C86A-UBE2T protein, an E2 activity-dead mutant, in which the 86th residue of cysteine was replaced with alanine. (aacrjournals.org)
  • Although its common function is seen as binding and repressing E2F targets, Rb is likely a multifunctional protein as it binds to at least 100 other proteins. (wikipedia.org)
  • BRCA1 promotes homologous recombination-mediated DNA repair (HRR). (aacrjournals.org)
  • e mutações missense , associada a formação de uma proteína BRCA1 não funcional. (wikipedia.org)
  • Basicamente essa população apresentava uma mutação missense que acarretava na substituição de uma cisteína por uma glicina em uma região importante da proteína , conhecida como domínio ring, dificultando a capacidade de estabelecimento de ligação da proteína BRCA1. (wikipedia.org)
  • IN an era of increasingly widespread genetic testing, DNA sequencing identifies many missense substitutions with unknown effects on protein function and disease risk. (genetics.org)
  • As a proof-of-concept, we initiated massively parallel functional analysis of BRCA1, a protein for which there are multiple biochemical functions as well as known pathogenic and benign missense substitutions to benchmark results. (genetics.org)
  • We assessed the effects of missense mutants on different stages of BRCA1-mediated DNA repair by homologous recombination using chicken lymphoblastoid DT40 cells as a model system. (sigmaaldrich.com)
  • Tudini E, Moghadasi S, Parsons MT, van der Kolk L, van den Ouweland AMW, Niederacher D, Feliubadaló L, Wappenschmidt B, Spurdle AB, Lazaro C. Substantial evidence for the clinical significance of missense variant BRCA1 c.5309G>T p. (harvard.edu)
  • BRCA1 PARsylation and/or RAP80 expression is defective in a subset of sporadic breast cancer cell lines and patient-derived tumor xenograft models. (aacrjournals.org)
  • Misregulation and reduced expression of BRCA1 also contribute to sporadic forms of breast cancer [ 5 ]. (hindawi.com)
  • BRCA1 and its toolbox for the maintenance of genome integrity. (nih.gov)
  • Thus, BRCA1 is emerging as the master regulator of the genome through its ability to execute and coordinate various aspects of the DNA damage response. (nih.gov)
  • [25] BRCA1 orthologs have been identified in most vertebrates for which complete genome data are available. (wikipedia.org)
  • When BRCA1 PARsylation is defective, it gives rise to excessive HRR and manifestations of genome instability. (aacrjournals.org)
  • mutated BRCA1 has been found in up to 75% of families with hereditary OC - Recent data suggest that dysfunction of BRCA1andBRCA2, so-called BRCAness, maybe more prevalent than originally assumed. (knowcancer.com)
  • Although the enzymatic substrates of BRCA1 are not fully defined, it does catalyze its own ubiquitination to generate polyubiquitinated BRCA1 isoforms that are not targeted for proteasomal degradation. (pubmedcentralcanada.ca)
  • Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. (mdpi.com)
  • 1. A protein that regulates normal cell growth and proliferation and prevents unrestrained division of cells whose DNA has been damaged, as from ultraviolet or ionizing radiation. (thefreedictionary.com)
  • Because of the functional analyses performed below, we designated this protein as Fanconi anemia-associated nuclease 1 (FAN1). (sciencemag.org)
  • Although functional analysis at this scale is made possible by deep mutational scanning ( Fowler and Fields 2014 ), a central challenge is that any single assay may not recapitulate all the activities of a given protein in human disease. (genetics.org)
  • Summary Curli are functional amyloid fibers that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria. (europa.eu)
  • 2015 ). Additional structural and functional features may be uniquely imparted to Id4 protein by a proline-rich region present in the C-terminus. (springer.com)
  • Rb belongs to the pocket protein family , whose members have a pocket for the functional binding of other proteins. (wikipedia.org)
  • Apweiler R, Attwood TK, Bairoch A et al (2001) The InterPro database, an integrated documentation resource for protein families, domains and functional sites. (springer.com)
  • A screen was performed to determine what genetic events would allow normal cells to tolerate loss of functional BRCA1 . (healthcanal.com)
  • Breast cancer type 1 susceptibility (BRCA1) protein is a tumor suppressor that is expressed in breast tissue cells and other tissues where it primarily functions to sense and repair DNA damage. (activemotif.jp)
  • Finally, we promote an insightful perspective regarding the clinical implication of the cytosolic noncanonical roles of FA proteins in cancer predisposition, suggesting that these alternative roles could be of critical importance for disease progression. (mdpi.com)
  • This entry includes animal BRCA1 (BREAST CANCER SUSCEPTIBILITY 1) proteins and their homologues from plants [ PMID: 22629260 ]. (ebi.ac.uk)
  • Regiões de aglomerados de mutações associadas ao câncer de mama (BCCRs - breast cancer cluster regions) foram encontradas para três regiões de BRCA1 (de acordo com a posição nucleotídica): c.179-c.505, c.4328-c.4945 e c.5261-c.5563. (wikipedia.org)
  • Strong genetic and epidemiologic links exist between BRCA1 HRR function and its breast cancer suppression activity ( 3-6 ). (aacrjournals.org)
  • Many proteins are involved in everyday DNA repair, but if they are mutated, the repair system breaks down and cancer can occur. (innovations-report.com)
  • In doing so, the protein helps our cells to mend damaged DNA and fix the sorts of faults that could eventually lead to cancer. (cancerresearchuk.org)
  • indeed, 80% response rates, including 45% complete responses in BRCA1 -mutated breast cancer, have been reported with cisplatin ( 3 ). (aacrjournals.org)
  • [7] [8] Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomaviruses , bind and inactivate pRb, this can lead to cancer. (wikipedia.org)
  • Furthermore, knocking down of UBE2T protein induced upregulation of BRCA1 protein in breast cancer cells, whereas its overexpression caused the decrease of the BRCA1 protein. (aacrjournals.org)
  • There is no evidence that BRCA1 is a direct, biologically relevant substrate for BAP1, and therefore, the biological function of BAP1 remains to be identified. (aacrjournals.org)
  • Studies support that BRCA1 exerts its tumour suppression function primarily through its involvement in cell cycle checkpoint control and DNA damage repair. (nih.gov)
  • Therefore, it becomes important for us to not only identify the phosphopeptide-binding domains and their substrates, but to also use systems biology approaches to understand the activation of different protein kinases as a function of time, in order to understand how signalling networks are coordinated in time and space. (hstalks.com)
  • We are interested in the structure, function and disease implications of the CIZ1 protein, and related factors involved in organisation of the mammalian cell nucleus. (findaphd.com)
  • Moreover, based on the presence of satellite DNA and the proteins HP1, BRCA1, ATRX and DAXX within the PML-NBs, we propose that these structures have a specific function: the re-establishment of the condensed heterochromatic state on late-replicated satellite DNA. (biologists.org)
  • Drost R, Bouwman P, Rottenberg S et al (2011) BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance. (springer.com)
  • Li M, Yu X (2013) Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation. (springer.com)
  • PARsylation is directed at the BRCA1 DNA binding domain and downmodulates its function. (aacrjournals.org)
  • Furthermore, HDACs promote the stability and function of proteins involved in the DNA damage response such as Ku70 and p53 ( 20-22 ). (aacrjournals.org)
  • Dr. Espen Spangenburg, associate professor of kinesiology, and his laboratory team are the first to identify that the BRCA1 protein is expressed in the skeletal muscle of both mice and humans, and that it plays a key role in fat storage, insulin response and mitochondrial function in skeletal muscle cells. (eurekalert.org)
  • BRCA1 is a Novel Regulator of Metabolic Function in Skeletal Muscle" was written by Kathyrn C. Jackson, Eva-Karin Gidlund, Jessica Norrbom, Ana P. Valencia, David M. Thomson, Rosemary A. Schuh, P. D. Neufer and Espen E. Spangenburg and published in the Journal of Lipid Research . (eurekalert.org)
  • The BRCA1 protein also has a DNA-binding domain [ 13 , 14 ] and an SQ-cluster domain (SCD) in its central region [ 15 ]. (mdpi.com)
  • A small molecule inhibitor (I-CBP112) binding to the bromodomain domain of CBP/p300 has been developed for leukemia therapy. (wikipedia.org)
  • ZEB and zfh-1 , both contain the sequence PLDLS in the same region of the repressor domain, and we demonstrate that this sequence binds CtBP-1 and -2. (pnas.org)
  • 16, 18 In NBS1, the MRE11 binding domain has been located to the extreme carboxyterminus of the protein, 16 and the corresponding site in RAD50 has been located to a 40 residue coiled coil region adjacent to the ABC domain. (bmj.com)
  • We show here using a pulldown assay with an internal standard that wild-type (WT) and mutant T6 sequences displayed similar ASF/SF2 binding efficiencies, which were significantly lower than that of a typical exonic splicing enhancer derived from the extra domain A exon of fibronectin. (asm.org)
  • PC4 consists of two domains: an N-terminal regulatory domain and a C-terminal cryptic DNA-binding domain. (ebi.ac.uk)
  • Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. (mit.edu)
  • Aravind L, Koonin EV (2001b) THUMP-a predicted RNA-binding domain shared by 4-thiouridine, pseudouridine synthases and RNA methylases. (springer.com)
  • Since ICP0 does not bind directly to DNA ( 13 ), it is likely that it functions via interactions with other proteins. (asm.org)
  • Thus, hyperfunctioning BRCA1 can elicit genomic abnormalities similar to those observed in the absence of certain BRCA1 functions. (aacrjournals.org)
  • Synthetic lethality occurs when a genetic defect or defective protein is compatible with cell viability, but is lethal when combined (i.e., synthesized) with another genetic/protein defect ( 1, 2 ). (aacrjournals.org)
  • BRCA1 helps ensure the stability of a normal cell's genetic makeup (DNA) by creating a protein that helps repair DNA damage. (healthcanal.com)
  • To address this, we have developed a proteomics approach to identify phosphoserine/phosphothreonine-binding domains that specifically recognize the phosphorylated sequences produced by the action of these protein kinases. (mit.edu)
  • 2014 ). Id proteins were described initially as inhibitors of differentiation and more recently as regulators of cell cycle progression, senescence, apoptosis, and tumorigenesis. (springer.com)
  • The p53 protein may then act to protect the cell by halting the cell cycle so that the DNA damage can be repaired, or, if the DNA damage is too severe, p53 protein can kill the cell by APOPTOSIS so that the defective DNA is not passed on. (thefreedictionary.com)
  • Following DNA damage, the tumor suppressor protein p53 has a crucial influence on whether cells will survive or die by either stimulating DNA repair or initiating apoptosis if the DNA damage has exceeded a certain threshold. (thefreedictionary.com)
  • One key protein that coordinates DNA repair with cell cycle progression and apoptosis is the tumor suppressor protein p53. (rupress.org)
  • We found that FAM35A is absent in a BRCA1-mutant tumor (HCC1937) with anomalous resistance to PARP inhibitors. (mdanderson.org)
  • This mutant BRCA1 provides significant insight into how BRCA1 engages the downstream components of homologous recombination. (mskcc.org)
  • What I'd like to tell you about is how phosphoserine and phosphothreonine binding domains are involved in orchestrating cells signaling with a particular focus on cell cycle control and the response to cells to DNA damage. (hstalks.com)
  • Required for protein stability of MTOR and MTOR-related proteins, and cell cycle progress by growth factors (PubMed:25657994). (genecards.org)
  • BRCA1 has a number of functions in the DNA damage response in mammalian cells, including signaling to cell-cycle checkpoints, and recruiting proteins involved in homologous recombination. (mskcc.org)
  • In particular, we study how modifications of proteins are involved in transmitting environmental signals to the cell cycle machinery. (mit.edu)
  • The BRCA proteins play an important role in the DNA repair mechanisms and are also involved in the control of the cell cycle checkpoints, in protein ubiquitinization and chromatin remodelling. (knowcancer.com)