Phosphorylation of brca1. Medical search. Frequent questions

Approximately 5-10% of all breast and ovarian cancers are thought to arise from a hereditary predisposition to the disease, 1 BRCA1 and BRCA2 being the most important susceptibility genes. (bmj.com)
F) ATR pathway signaling integrity after ATR, BRCA2 LP-533401 ic50 (B2) and BRCA1 (B1) depletion. (insulin-receptor.info)
G) Depletion of 53BP1 with shRNAs restores cell cycle arrest in BRCA1, FANCM, FANCJ and FANCL depleted cells however, not in ATR or BRCA2 depleted cells. (insulin-receptor.info)
H) Chemical substance inhibition of DNA-PKcs restores cell routine arrest in BRCA1, FANCM, FANCL and FANCJ depleted cells however, not in ATR or BRCA2 depleted cells. (insulin-receptor.info)
Although only 5 to 10% of breast cancer cases are inherited, recent estimates suggest that 55 to 65% of BRCA1 mutation carriers and approximately 45% of BRCA2 mutation carriers will develop breast cancer by age 70. (telesisbio.com)
It is well established that BRCA1 and BRCA2 proteins play a crucial role in maintaining genomic integrity through DNA repair by homologous recombination. (telesisbio.com)
Indeed, during the process of mitosis, BRCA2 is a target of phosphorylation by Polo-like kinase 1 (PLK1), both in its N-terminal region and in its central region, although the functional role of these phosphorylation events remains unclear. (telesisbio.com)
The regulatory effects of BRCA on GR were assessed in 146 serous ovarian cancer patients (28 pairs of BRCA1-mutated or not, 23 pairs of BRCA2-mutated or not, and 22 pairs with hypermethylated BRCA1 promoter or not). (biomedcentral.com)
Fresh tumor samples, adjacent normal ovarian tissues, ascites, and blood samples were obtained at the time of primary surgery before any chemotherapy or radiotherapy (28 pairs of BRCA1-mutated or not, 23 pairs of BRCA2-mutated or not, and 22 pairs with hypermethylated BRCA1 promoter or not). (biomedcentral.com)
BRCA1 and BRCA2 play essential roles in repairing DNA double strand breaks and a deficiency of BRCA proteins sensitizes cancer cells to PARP inhibition," said Hung. (medicalxpress.com)
La proteína FANCD2 modificada interacciona con la PROTEÍNA BRCA2 en un complejo estable con CROMATINA, y está implicada en la REPARACIÓN DEL ADN mediante RECOMBINACIÓN homóloga. (bvsalud.org)

6, 7 BRCA1 interacts with a variety of proteins and is involved in multiple cellular processes including DNA repair, transcription, and checkpoint control. (bmj.com)
8- 10 In attempts to identify new breast and ovarian cancer susceptibility genes, much research has focused on BRCA1 associated proteins. (bmj.com)
11 Both proteins possess an N-terminal RING finger motif and two BRCA1 C-terminal (BRCT) domains present in numerous proteins involved in DNA repair and cell cycle regulation. (bmj.com)
11 The functionally important BARD1/BRCA1 heterodimer formation is mediated by the RING finger motifs and has also been shown to markedly increase the stability of both proteins. (bmj.com)
BARD1, unlike BRCA1, also contains a centrally located sequence of three ankyrin repeats 11 that are found in many proteins involved in transcriptional regulation. (bmj.com)
The phenotype of Bard1 null mice was found to be remarkably similar to that of Brca1 nulls, further emphasising the functional relationship between these two proteins. (bmj.com)
the protein levels of UHRF1 and BRCA1 were measured with western blot or cell immunofluorescent staining, and the interaction of UHRF1 and BRCA1 proteins was detected with co-immunoprecipitation when cells were treated with drugs. (biomedcentral.com)
In addition, downregulation of active mRNA processing and RNA splicing proteins were also observed in BRCA1 mut tumours. (bmj.com)
The best studied effector proteins binding phosphorylated histones are 14-3-3 proteins and BRCA1 C-terminus (BRCT) domains. (musculoskeletalkey.com)

The p53 protein regulates Brca1 transcription both in vitro and in vivo, and Brca1 participates in p53 accumulation after gamma-irradiation through regulation of its phosphorylation and Mdm2 expression. (nih.gov)
25 BARD1 also regulates the subcellular localisation of BRCA1, both by translocating BRCA1 into the nucleus and by inhibiting its nuclear export. (bmj.com)
L ike protein phosphorylation by kinases, protein ubiquitylation regulates many aspects of cell function and provides a wealth of drug target opportunities across many therapeutic areas including cancer, cardiovascular, metabolism, inflammation, neurodegeneration and infectious diseases. (ddw-online.com)
Phosphorylation of serine 367 of FOXC2 by p38 regulates ZEB1 and breast cancer metastasis, without impacting primary tumor growth. (tamu.edu)

Our biochemical and genomic analyses showed that the BRCA1-BARD1 complex interacts with TOP2B in the EGR1 transcription start site and in a large number of protein-coding genes. (elsevierpure.com)
Mutations in splicing elements, for example, have been found in genes such as LKB1 , KIT , CDH17 , KLF6 and BRCA1 , and changes in trans-acting regulators can affect the expression of genes such as Ron , RAC1 and CD44 . (biologists.com)

We are investigating the impact of specific classes of gene mutations, such as ATM, BRCA1, and MYBL2 on genome integrity. (birmingham.ac.uk)
About 8% of cases are hereditary, and approximately half of these are associated with germline mutations of the breast tumor suppressor gene BRCA1 (refs. (nih.gov)
11- 13 The finding of breast cancer associated mutations within the RING finger domain of BRCA1 , disrupting BRCA1/BARD1 interaction, 11, 14 and the occurrence of BARD1 missense mutations in breast cancer patients, 15- 17 implies participation of BARD1 in BRCA1 mediated tumour suppression. (bmj.com)
Mutations of Tyr residues on OCLN showed the role of Tyr phosphorylation in regulating OCLN. (biomedcentral.com)

DUSP3 regulated OCLN ubiquitination and degradation through decreasing OCLN tyrosine phosphorylation directly or through suppressing focal adhesion kinase, the OCLN kinase. (biomedcentral.com)
Intriguingly, the BRCA1-BARD1 complex ubiquitinates TOP2B, which stabilizes TOP2B binding to DNA while BRCA1 phosphorylation at S1524 controls the TOP2B ubiquitination by the complex. (elsevierpure.com)
Phosphorylation and ubiquitination of oncogenic mutants of beta-catenin containing substitutions at Asp32. (tamu.edu)
DSBs elicit a signalling cascade that modifies the chromatin surrounding the break, first by ATM-dependent phosphorylation and then by RNF8-, RNF168- and BRCA1-dependent regulatory ubiquitination. (elsevierpure.com)
2 In addition to the well-established epigenetic role of DNA methylation, this definition includes a variety of more transient histone modifications such as acetylation, methylation, or phosphorylation that underlie epigenetic effects, and that will be discussed in this chapter along with the influence of SUMOylation, ubiquitination, adenosine diphosphate (ADP) ribosylation, and microRNA. (musculoskeletalkey.com)

1) How does the hereditary breast tumor suppressor BRCA1 interaction network suppress breast tumor development? (mdanderson.org)
BARD1 was originally identified through its interaction with BRCA1, with which it has a closely related domain structure. (bmj.com)
21 Furthermore, interaction between the BARD1/BRCA1 heterodimer and cleavage stimulation factor subunit 1 (CSTF1, also called CstF-50) represses the polyadenylation machinery, presumably to prevent inappropriate mRNA processing at sites of DNA repair. (bmj.com)
26 The suggested role in TP53 dependent apoptotic signalling 27 and interaction with the ankyrin repeats of proto-oncoprotein BCL3, thereby possibly modulating the activity of transcription factor NFKB, 28 represent BRCA1 independent functions of BARD1. (bmj.com)
Here, we report a stepwise recruitment of yeast NuA4 to DSBs first by a DNA damage-induced phosphorylation-dependent interaction with the Xrs2 subunit of the Mre11-Rad50-Xrs2 (MRX) complex bound to DNA ends. (uthscsa.edu)
BRCA1 is recognized to function and play an essential function throughout mitosis by preventing inappropriate centrosome amplification via the interaction of hypo-phosphorylated BRCA1 with -tubulin [35, 36]. (calcium-channel.com)
In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites. (cusabio.com)

We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases. (mdanderson.org)
In this study, we show that Tip60 is required for the early DNA damage response (DDR) to UV, including the phosphorylation of histone 2AX, c-Jun N-terminal kinases (JNKs), and ataxia telangiectasia-related substrates. (rupress.org)
We found that BRCA1 is phosphorylated at S1524 by the kinases ataxia-telangiectasia mutated and ATR during gene activation, and that this event is important for productive transcription. (elsevierpure.com)
FANCD2 is a phosphorylation target of kinases ATM and perhaps ATR, a phosphorylation that is necessary to maintain the S-phase checkpoint. (kupferlab.org)

BRCA1 mutation status was known for all patients (BRCA1 mut and BRCA1 wt ). (bmj.com)
Comprehensive network analysis was performed comparing both healthy and cancer tissues based on their BRCA1 mutation status. (bmj.com)
Absence or mutation of BRCA1 has been associated with development and progression of breast cancer. (snu.ac.kr)

oxidative phosphorylation. (palomid529.com)
Combined oxidative phosphorylation defect type 4 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by a neonatal onset of severe metabolic acidosis and respiratory distress, persistent lactic acidosis with episodes of metabolic crises, developmental regression, microcephaly, abnormal gaze fixation and pursuit, axial hypotonia with limb spasticity and reduced spontaneous movements. (mendelian.co)
Combined Oxidative Phosphorylation Defect Type 4 Is also known as coxpd4. (mendelian.co)
Combined oxidative phosphorylation deficiency type 4 (sequence analysis of TUFM gene). (mendelian.co)

Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. (cusabio.com)

This protective effect of preaccumulated p53 was mediated, at least in part, by the increased expression of CDKN1A/p21, subsequent down-regulation of BRCA1, and impaired JNK activation accompanied by decreased association of replication protein A with chromatin. (rupress.org)
Diminished phosphorylation of Akt in GPR30-siRNA transfected HCC1937 cells suggests regulation of Akt signaling by GPR30. (snu.ac.kr)
Genistein caused cell cycle arrest at the G2/M phase in BRCA1 mutant cells, leading to down-regulation of Cyclin B1. (snu.ac.kr)
Together, these findings suggest the novel function of the BRCA1-BARD1 complex in the regulation of TOP2B and Pol II-mediated gene expression. (elsevierpure.com)

Also, in response to IONIZING RADIATION it can undergo PHOSPHORYLATION by ataxia telangiectasia mutated protein. (bvsalud.org)

Introduction/Background Our understanding of the molecular events associated to the development of high-grade serous ovarian cancer (HGSOC) in BRCA1 mutated patients and the differences observed in treatment response remain to be elucidated. (bmj.com)

Genistein induces G2/M phase arrest by down-regulating Cyclin B1 expression through suppression of Akt phosphorylation and GPR30 activation in BRCA1 deficient breast cancer cells. (snu.ac.kr)
BRCA1 knockdown was effective at inhibiting GR expression, and overexpression of BRCA1 induces an increase in GR levels in ovarian cancer cells. (biomedcentral.com)

Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity. (tamu.edu)

BRCA1 promoter methylation was analyzed by bisulfite sequencing using primers flanking the core promoter region. (biomedcentral.com)

I examined the effects of genistein on proliferation and growth of TNBC cells, and how these effects differ depending on the presence or absence of functionally active BRCA1. (snu.ac.kr)

These results indicate that deficiency in BRCA1 promotes aggressive proliferation of breast cancer. (snu.ac.kr)

Here, we sought to elucidate the underlying mechanism(s) using mice deficient in the Brca1 exon 11 isoform (Brca1Delta11/Delta11). (nih.gov)
BRCA1 deficient breast cancer cells showed increased cell proliferation compared to breast cancer cells harboring wild-type BRCA1. (snu.ac.kr)
Furthermore, BRCA1 deficient breast cancer cells had greater accumulation of intracellular reactive oxygen species (ROS), which was associated with a low Nrf2 mRNA level. (snu.ac.kr)
Genistein was chosen to be tested as a representative phytochemical that might inhibit aggressive proliferation of BRCA1 deficient TNBC cells by inactivating GPR30. (snu.ac.kr)
OCLN had an increased phosphorylation level in DUSP3-deficient cells. (biomedcentral.com)

We quantitatively evaluated the protein changes and post-translational modifications focusing in the phosphorylation and ubiquitylation events. (bmj.com)

Colocalisation of BARD1 with BRCA1 and RAD51 in response to DNA damage indicates a role in DNA repair, 19, 20 which is supported by the recent observation of BARD1 participation along with BRCA1 in homology directed repair of chromosome breaks. (bmj.com)
22, 23 The significance of BARD1/BRCA1 collaboration has also been emphasised by studies of its ubiquitin ligase activity that might contribute to tumour suppression and other biological functions of BRCA1. (bmj.com)
Here, we report a novel function of the breast cancer 1 (BRCA1)-BRCA1-associated ring domain 1 (BARD1) complex in this process. (elsevierpure.com)

Within the core complex, both FANCA and FANCG are phosphorylated (P). In the presence of an intact core complex, FANCD2 is monoubiquitinated (Ub) on K561 and colocalizes in nuclear foci with BRCA1, where it carries out its roles in DNA repair and/or cell cycle control. (kupferlab.org)

Within the absence of any DNA harm, we located that BRCA14P cells spent considerably a lot more time in all phases of mitosis relative to BRCA1 wild-type (Figure 5A). (calcium-channel.com)
Furthermore, we found that though cells complemented with wild-type BRCA1 demonstrated a baseline level of mitotic aberrations, cells expressing BRCA14P had drastically (3-fold) enhanced levels above wild-type and a trend of 30 elevated levels above vector handle (Figure 5B), suggesting that BRCA14P produces extra insult to mitosis than having no BRCA1 at all. (calcium-channel.com)
This shift within the excellent of DSB repair, coupled with an inadequate G2/M arrest, permits excessively damaged cells to inappropriately try mitosis, therefore facilitating chromosomal instability and resulting in mitotic catastrophe.DISCUSSIONIt was previously recommended that the radiosensitivity of BRCA1-defective cells isn't completely attributable to impaired cell cycle checkpoints [25]. (calcium-channel.com)
As a result, lack of BRCA1 SQ-cluster phosphorylation is likely to have an effect on mitosis and beyond. (calcium-channel.com)
To address this, scientists from the Institut Curie in France elucidated how this phosphorylation contributes to mitosis control. (telesisbio.com)

Mechanistically, veliparib or SAHA alone reduced BRCA1 or UHRF1 protein levels, co-treatment with veliparib and SAHA synergistically reduced BRCA1 protein levels by targeting the UHRF1/BRCA1 protein complex, the depletion of UHRF1 resulted in the degradation of BRCA1 protein, while the elevation of UHRF1 impaired co-treatment-reduced BRCA1 protein levels. (biomedcentral.com)

In this study, I investigated the proliferation signaling pathway in triple negative breast cancer (TNBC) cells with respect to the presence of functional BRCA1 and whether this signaling can be inhibited by genistein. (snu.ac.kr)
Elevated expression of cell proliferation targets P-Akt and GPR30 was observed in BRCA1 mutated HCC1937 cells. (snu.ac.kr)
Taken together, lack of functional BRCA1 activates GPR30 signaling, thereby phosphorylating Akt and promoting cell proliferation. (snu.ac.kr)

Inhibition of nuclear import of Large T antigen by phosphorylation-dependent (T124) binding of BRCA1-associated protein (BRAP) . (eu.org)

We recently discovered new ways the BRCA1 gene functions which could help expand our understanding of the development of ovarian and breast cancers. (birmingham.ac.uk)
2, 3 Genomic alterations in BRCA1 are found in 40-50% of families with a high incidence of breast cancer (six or more cases), and in a majority (75-80%) of the families that display both breast and ovarian cancers. (bmj.com)

Two human breast cancer cell lines, MDA-MB-231 (wild-type BRCA1) and HCC1937 (mutated BRCA1), were compared to ascertain the difference in growth signaling depending on the presence of functional BRCA1. (snu.ac.kr)

Additionally, MDA-MB-231 cells were transfected with BRCA1-siRNA for gene silencing to verify whether the difference was truly due to BRCA1. (snu.ac.kr)

Nevertheless, additional cellular functions of BRCA1 in ovarian cancer are poorly understood. (bmj.com)
However, dynamic cross-talk between BRCA1 and GR signaling pathways are poorly understood. (biomedcentral.com)

Cancer tissues harvesting BRCA1 mut showed specific changes related to DNA damage repair and activated mTOR and insulin signalling pathways. (bmj.com)

Our studies revealed that the synergistic lethality of HDAC and PARP inhibitors resulted from promoting DNA damage and inhibiting HR DNA damage repair pathways, in particular targeting the UHRF1/BRCA1 protein complex. (biomedcentral.com)

We have previously reported a mouse model in which Brca1 exon 11 is eliminated in mammary epithelial cells through Cre-mediated excision. (nih.gov)

These findings provide a mechanism for BRCA1-associated breast carcinogenesis. (nih.gov)

Genistein treatment also decreased the level of phosphorylated Akt, an upstream kinase of Cyclin B1, more prominently in BRCA1 mutated breast cancer cells. (snu.ac.kr)

Cells collected at the indicated times after IR (10 Gy) were examined for Chk1 phosphorylation. (insulin-receptor.info)
In addition, BRCA1 silenced MDA-MB-231 cells, when injected into nude mice, were capable of forming larger tumors. (snu.ac.kr)
Likewise, MDA-MB-231 cells that were transfected with BRCA1-siRNA were more susceptible to genistein-mediated growth inhibition. (snu.ac.kr)
For example, in cultured human being umbilical vein endothelial cells (HUVEC) physiological concentrations of VEGF attenuated TGF-related phosphorylation of Smad2/3 [9]. (palomid529.com)
The knockdown and overexpression of BRCA1 were achieved using a lentiviral vector in 293 T cells, SKOV3 ovarian cancer cells, and primary non-mutated and BRCA1-mutated ovarian cancer cells. (biomedcentral.com)

These results suggest that GR may be a potential target for BRCA1 in ovarian cancer progression. (biomedcentral.com)

Rather, someimpactjournals.com/oncotargetfunction of BRCA1 - besides its intra-S and/or G2/M checkpoint activity - affects cell survival immediately after IR. (calcium-channel.com)

In addition, in some patients with a personal or family history of breast and ovarian cancer, the protective role of BRCA1 in DNA-copying is disabled - while its break repair function is still active. (birmingham.ac.uk)

The physiological relevance of E2F1 in the DNA damage response is now being explored using a novel knock-in mouse model we developed that blocks E2F1 phosphorylation by ATM/ATR. (mdanderson.org)

Results showed BRCA1 changes shape in order to protect vulnerable DNA until the copying machinery can be restarted. (birmingham.ac.uk)

Regression analysis was used to examine the possible relationship between BRCA1 and GR expression levels. (biomedcentral.com)

Finally, a deeper understanding of the RNA splicing events related to BRCA1 could unveil new clinically relevant cellular processes in ovarian cancer. (bmj.com)

Anatomy23

Organisms8

Diseases5

Chemicals and Drugs144

Analytical, Diagnostic and Therapeutic Techniques and Equipment17

Phenomena and Processes55

Disciplines and Occupations1

Information Science3

Named Groups1

Health Care1

BRCA211

Proteins9

Regulates4

Genes2

Mutations4

Ubiquitination5

Interaction7

Kinases4

Mutation3

Oxidative phosphorylation4

DSBs1

Regulation4

Ataxia-telangi1

Serous ovarian cancer1

Induces2

Transcriptional1

Methylation1

Functionally1

Deficiency1

Deficient5

Ubiquitylation1

BARD13

FANCD21

Mitosis5

Depletion1

Proliferation3

Nuclear1

Cancers2

Functional1

Additionally1

Poorly understood2

Tissues1

Complex1

Epithelial1

Findings1

Breast cancer1

Cells5

Progression1

Survival1

Repair1

Response1

Results1

Examine1

Cellular1