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  • MAPK
  • In addition, signaling studies show p38 mitogen-activated protein kinase (MAPK) as the upstream regulator of Sp1-mediated activation of the caveolin-1 promoter following oxidative stress. (aacrjournals.org)
  • Inhibition of p38 MAPK prevents the oxidant-induced Sp1-mediated up-regulation of caveolin-1 protein expression and development of premature senescence. (aacrjournals.org)
  • Phosphorylation of Thr at position 148 is detected in response to various stress conditions such as UV irradiation, oxidative stress, and anisomycin treatment or JDP2 is also regulated by other kinases such as p38 MAPK and doublecortin like protein kinase. (wikipedia.org)
  • A link between VDR and the RAS-mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)-AKT pathway has been suggested. (nih.gov)
  • cellular senescence
  • Consistent with this idea, we have previously shown that overexpression of caveolin-1 is sufficient to arrest mouse embryonic fibroblasts in the G 0 -G 1 phase of the cell cycle, reduce their proliferative life span, and promote premature cellular senescence through activation of a p53/p21-dependent pathway ( 33 , 34 ). (aacrjournals.org)
  • For instance, 14-3-3ζ controls cellular senescence by complexing with BIS to chaperone protein folding of STAT3 and activate the signaling pathway. (wikipedia.org)
  • kinase
  • Serine/threonine-protein kinase PAK 5 is an enzyme that in humans is encoded by the PAK5 gene. (wikipedia.org)
  • Telerman A, Amson R, Zakut-Houri R, Givol D (1988) Identification of the human pim-1 gene product as a 33-kilodalton cytoplasmic protein with tyrosine kinase activity. (springer.com)
  • Once it is allosterically activated, it recruits and activates proteins necessary for the propagation of growth factors , as well as other cell signaling receptors like c-Raf and PI 3-kinase . (wikipedia.org)
  • Calcitriol induces a significant G 0 /G 1 arrest and modulates p21 Waf1/Cip1 and p27 Kip1 , the cyclin dependent kinase inhibitors. (springer.com)
  • The disease is due to conversion of the tightly regulated tyrosine kinase of ABL1 protein to being unregulated and continuously active in the BCR-ABL1 fusion protein. (wikipedia.org)
  • p16 (also known as cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 and as several other synonyms), is a tumor suppressor protein, that in humans is encoded by the CDKN2A gene. (wikipedia.org)
  • epigenetic
  • Substantial evidence shows that alteration in the expression of NF-kB-induced proinflammatory cytokine TNF- α and interleukins, oncogenes, and tumour suppressor genes typically follows chronic hepatic inflammation associated with epigenetic aberrations [ 5 ]. (hindawi.com)
  • Deeper understanding of epigenetic aberrations, their interconnectivity, and clinical phenotypes in HCC patients may provide useful insights in the development of novel and more effective biomarkers for HCC treatment and better prognosis. (hindawi.com)
  • Regulation of p16 is complex and involves the interaction of several transcription factors, as well as several proteins involved in epigenetic modification through methylation and repression of the promoter region. (wikipedia.org)
  • heat shock pr
  • Prior to these studies, the only biochemical function attributed to p53 was its binding to heat shock proteins. (wikipedia.org)
  • The binding of an androgen to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization. (wikipedia.org)
  • encode
  • At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4. (wikipedia.org)
  • apoptotic
  • Calcitriol induces PARP cleavage, increases the bax/bcl-2 ratio, reduces levels of phosphorylated mitogen-activated protein kinases (P-MAPKs, P-Erk-1/2) and phosphorylated Akt (P-Akt), induces caspase-dependent MEK cleavage and up-regulation of MEKK-1, all potential markers of the apoptotic pathway. (springer.com)
  • In combination with calcitriol, dexamethasone results in a significant time- and dose-dependent increase in VDR protein and an enhanced apoptotic response as compared to calcitriol alone. (springer.com)
  • In particular, 14-3-3ζ is a key player in regulating cell survival and interacts with many apoptotic proteins, including Raf kinases, BAX, BAD, NOXA, and caspase-2. (wikipedia.org)
  • The14-3-3 protein zeta/delta (14-3-3ζ) is a protein (in humans encoded by the YWHAZ gene on chromosome 8) with an important apoptotic constituents. (wikipedia.org)
  • apoptosis
  • Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. (wikipedia.org)
  • Expression
  • Western blotting analysis was used to detect the expression of proteins. (springer.com)
  • The expression of CDK4, cyclin D1, and phospho-Rb was markedly decreased in the A549-shTGIF cells compared with the A549-shcon cells, and p21 was markedly increased in the A549-shTGIF cells compared with the A549-shcon cells. (springer.com)
  • A lower level of β-Catenin protein expression was observed in the A549-shTGIF cells than that in the A549-shcon cells. (springer.com)
  • GATA-binding protein 3 (GATA3) is a transcription factor that is highly expressed in normal breast luminal epithelium and the luminal A tumor subtype that has been defined in studies of gene expression patterns ( 1 - 5 ). (aacrjournals.org)
  • 9 ) have shown that GATA3 protein expression in tumors predicted prognosis. (aacrjournals.org)
  • have also shown that among ER-positive tumors, GATA3 protein expression seems to predict tumor estrogen responsiveness ( 10 ). (aacrjournals.org)
  • This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. (wikipedia.org)
  • PRC1 and PRC2 are two protein complexes that modify the expression of p16 through the interaction of various transcription factors that execute methylation patterns that can repress transcription of p16. (wikipedia.org)
  • degradation
  • These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S subunits, preventing random protein-enzyme encounter and uncontrolled protein degradation. (wikipedia.org)
  • The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, open the gate of 20S core particle, and guide the substate into the proteolytic chamber. (wikipedia.org)
  • Phosphorylation of cyclin D1's threonine residue T286 marks the protein for export from the nucleus and proteolytic degradation. (wikipedia.org)
  • The ARF product functions as a stabilizer of the tumor suppressor protein p53, as it can interact with and sequester MDM2, a protein responsible for the degradation of p53. (wikipedia.org)
  • pathway
  • The protein encoded by this gene is a component of the SMAD pathway, which regulates cell growth and differentiation through transforming growth factor-beta (TGFB). (cancerindex.org)
  • binds
  • In the absence of ligand, the encoded protein binds to the promoter region of TGFB-responsive genes and recruits a nuclear repressor complex. (cancerindex.org)
  • Normally, CDK4/6 binds cyclin D and forms an active protein complex that phosphorylates retinoblastoma protein (pRB). (wikipedia.org)
  • proteolysis
  • To meet such complicated demands in biological process via spatial and temporal proteolysis, protein substrates have to be recognized, recruited, and eventually hydrolyzed in a well controlled fashion. (wikipedia.org)
  • cyclin
  • Cyclin-D1 is a protein that in humans is encoded by the CCND1 gene. (wikipedia.org)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (wikipedia.org)
  • Cyclin D1 is a protein required for progression through the G1 phase of the cell cycle. (wikipedia.org)
  • Cyclin D1-CDK4 also enables the activation of cyclin E-CDK2 complex by sequestering Cip/Kip family CDK inhibitory proteins p21 and p27, allowing entry into the S phase. (wikipedia.org)
  • subunits
  • To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special degradative tag, the ubiquitinylation. (wikipedia.org)
  • This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. (wikipedia.org)
  • Mitogenic
  • A genome-wide RNAi screen reveals a trio-regulated rho GTPase circuitry transducing Mitogenic signals initiated by G protein-coupled receptors. (thermofisher.com)
  • exons
  • The PAK5 gene, the longest among the PAK family, contains a total of 12 exons of which four exons are for 5'-UTR and remaining 8 exons for protein coding(Gene from review). (wikipedia.org)
  • variants
  • Alternatively spliced transcript variants encoding the same protein have been described. (wikipedia.org)
  • this transcript contains an alternate open reading frame (ARF) that specifies a protein that is structurally unrelated to the products of the other variants. (wikipedia.org)
  • Clinical
  • Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. (wikipedia.org)
  • accumulation
  • Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. (wikipedia.org)
  • Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. (wikipedia.org)
  • recruits
  • It contains putative SUMO modification of lysine (Lys) residue at position 65, and recruits interferon regulatory factor 2 binding protein 1 (IRF2BP1), which acts as an E3 ligase. (wikipedia.org)
  • bind
  • In addition to these primary interactions, the target protein can also bind outside the groove via secondary interactions. (wikipedia.org)
  • regulatory
  • Other proteins such as interferon regulatory factor-2-binding protein-1 (IRF2BP1). (wikipedia.org)
  • According to the protein interaction and topological characteristics of this multisubunit complex, the 19S regulatory particle is composed of a base and a lid subcomplex. (wikipedia.org)
  • kinase
  • The inhibitor of p38 mitogen-activated protein kinase, SB239023, abrogated the inhibitory effect of fish oil on ILK expression, whereas the inhibitor of extracellular signal-regulated kinase, PD98059, had no effect. (aacrjournals.org)
  • Taken together, these findings show that fish oil inhibits ILK expression through activation of PPARγ-mediated and p38 mitogen-activated protein kinase-mediated induction of AP-2α. (aacrjournals.org)
  • Specifically, under growth-limiting conditions, ( a ) GSTP1 protected HCT116 cells from oxidative stress and associated apoptosis and ( b ) promoted mitogen-activated protein kinase-extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase-mediated G 1 -S cell cycle progression. (aacrjournals.org)
  • We have studied the roles of mitogen-activated protein kinase family in the antiproliferative effect of GnRHa on the Caov-3 human ovarian cancer cell line. (aacrjournals.org)
  • Although GnRHa had no effect on the activation of the Jun N-terminal kinase (JNK), treatment of Caov-3 cells with GnRHa activated extracellular signal-regulated protein kinase (ERK), and its effect was more than that induced by GnRH. (aacrjournals.org)
  • GnRHa also activated ERK kinase (mitogen-activated protein/ERK kinase) and resulted in an increase in phosphorylation of son of sevenless (Sos), and Shc. (aacrjournals.org)
  • Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the β-adrenergic receptor kinase I, which specifically blocks signaling mediated by the βγ subunits of G proteins, blocked the GnRHa-induced ERK activation. (aacrjournals.org)
  • Phorbol 12-myristate 13-acetate (PMA) also induced the ERK activity, but pretreatment of the cultured cells with PMA to down-regulate protein kinase C did not abolish the activation of ERK by GnRHa. (aacrjournals.org)
  • To examine the role of ERK cascade in the antiproliferative effect of GnRHa, PD98059, an inhibitor of mitogen-activated protein/ERK kinase, was used. (aacrjournals.org)
  • These results provide evidence that GnRHa stimulation of ERK activity may be mediated by Gβγ protein, not by PMA-sensitive protein kinase C nor extracellular Ca 2+ in the Caov-3 human ovarian cancer cell line, suggesting that this cascade may play an important role in the antiproliferative effect of GnRHa. (aacrjournals.org)
  • HspB1 is a protein of 205 amino acids (22783 Da), which can be phosphorylated at serines 15, 78 and 82 by mitogen- activated protein kinases associated protein kinases ( MAPKAP kinase 2 , MAPKAP kinase 3 ). (atlasgeneticsoncology.org)
  • PKCι promotes the transformed growth of pancreatic cancer cells through activation of the proliferative Rac1-mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK1/2 signaling pathway. (aacrjournals.org)
  • Phosphorylation of Thr at position 148 is detected in response to various stress conditions such as UV irradiation, oxidative stress, and anisomycin treatment or JDP2 is also regulated by other kinases such as p38 MAPK and doublecortin like protein kinase. (wikipedia.org)
  • Once it is allosterically activated, it recruits and activates proteins necessary for the propagation of growth factors, as well as other cell signaling receptors like c-Raf and PI 3-kinase. (wikipedia.org)
  • The disease is due to conversion of the tightly regulated tyrosine kinase of ABL1 protein to being unregulated and continuously active in the BCR-ABL1 fusion protein. (wikipedia.org)
  • heat shock pr
  • HspB1 belongs to the ubiquitous family of small heat shock proteins (sHsps). (atlasgeneticsoncology.org)
  • Prior to these studies, the only biochemical function attributed to p53 was its binding to heat shock proteins. (wikipedia.org)
  • The binding of an androgen to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization. (wikipedia.org)
  • apoptosis
  • The p53 tumour suppressor protein is considered the guardian of the genome and has a number of biological functions including cell cycle arrest, DNA repair, and apoptosis in response to various stresses, such as ultraviolet irradiation, serum deprivation, and exposure to anticancer drugs. (ubc.ca)
  • Expression of an activated K- ras oncogene caused cells treated with either sulindac sulfide or sulfone to undergo apoptosis earlier than nontransfected controls. (aacrjournals.org)
  • The DFMO-dependent decrease in colony formation in K- ras -activated cells occurred in the absence of apoptosis. (aacrjournals.org)
  • These data indicate that K- ras can influence the kinetics of apoptosis induction by sulindac metabolites and cell survival in response to DFMO. (aacrjournals.org)
  • KRAS
  • KRAS acts as a molecular on/off switch, using protein dynamics. (wikipedia.org)
  • citation needed] In turn, KRAS can bind to proteins of the Guanine Nucleotide Exchange Factor (GEF) class (such as SOS1), which forces the release of bound nucleotide (GDP). (wikipedia.org)
  • Subsequently, KRAS binds GTP present in the cytosol and the GEF is released from ras-GTP. (wikipedia.org)
  • mammalian
  • The mammalian Notch proteins (Notch1 to 4) are membrane-bound type I receptors with a large extracellular domain involved in ligand binding, and a cytoplasmic domain responsible for signal transduction. (beds.ac.uk)
  • vivo
  • Neural stem/progenitor cell (NPC)-specific constitutive Ras activation in vivo plus p53 deficiency led to development of primarily anaplastic astrocytoma (grade III), whereas combined loss of p53 plus p16 Ink4a /p19 Arf led to development of GBM (grade IV) at 100% penetrance within 6 weeks. (aacrjournals.org)
  • Furthermore, Alcantara Llaguno and colleagues ( 7 ) have shown that inactivation of Nf1 combined with loss of other tumor suppressors ( p53 and Pten ) in neural stem/progenitor cells (NPC), but not in non-NPCs, was both necessary and sufficient to induce glioma formation, indicating critical roles for Ras activation in NPCs on gliomagenesis in vivo . (aacrjournals.org)
  • mRNA
  • CP-31398 upregulated Bax and Bak mRNA and protein levels, altered mitochondrial membrane potential leading to the release of cytochrome c and activation of caspases-9 and -3. (ubc.ca)
  • degradation
  • The ARF product functions as a stabilizer of the tumor suppressor protein p53, as it can interact with and sequester MDM2, a protein responsible for the degradation of p53. (wikipedia.org)
  • These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S subunits, preventing random protein-enzyme encounter and uncontrolled protein degradation. (wikipedia.org)
  • The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, open the gate of 20S core particle, and guide the substate into the proteolytic chamber. (wikipedia.org)
  • molecular
  • Our findings suggest that the regulation of c-Myc in breast cancer cells is dependent on the molecular subtype, and that β-catenin-mediated regulation of c-Myc and p21 may control the balance of cell death and proliferation in breast cancer. (pubmedcentralcanada.ca)
  • sHsps bind denatured proteins and facilitate their refolding by the ATP-dependent molecular chaperones of the Hsp70 family (Haslbeck et al. (atlasgeneticsoncology.org)
  • epigenetic
  • Regulation of p16 is complex and involves the interaction of several transcription factors, as well as several proteins involved in epigenetic modification through methylation and repression of the promoter region. (wikipedia.org)
  • interferon regula
  • In this study, we ectopically expressed the interferon regulatory factor (IRF)-1 protein in the breast carcinoma cell lines MDA-MB-468 and SK-BR-3 using a recombinant adenovirus (Ad-IRF-1). (aacrjournals.org)
  • It contains putative SUMO modification of lysine (Lys) residue at position 65, and recruits interferon regulatory factor 2 binding protein 1 (IRF2BP1), which acts as an E3 ligase. (wikipedia.org)
  • Other proteins such as interferon regulatory factor-2-binding protein-1 (IRF2BP1). (wikipedia.org)
  • transcription
  • Up-regulation or activation of transcription results in increased synthesis of messenger RNA, which, in turn, is translated by ribosomes to produce specific proteins. (wikipedia.org)
  • The Jun dimerization protein is a member of the AP-1 family of transcription factors. (wikipedia.org)
  • JDP2 functions as a transcription activator or repressor depending on the leucine zipper protein member it is associated with. (wikipedia.org)
  • cellular
  • The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). (wikipedia.org)
  • proteolysis
  • To meet such complicated demands in biological process via spatial and temporal proteolysis, protein substrates have to be recognized, recruited, and eventually hydrolyzed in a well controlled fashion. (wikipedia.org)
  • cell
  • HspB1 was also detected as a surface membrane protein in some cancer cell types (Shin et al. (atlasgeneticsoncology.org)
  • Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length. (wikipedia.org)
  • In particular, 14-3-3ζ is a key player in regulating cell survival and interacts with many apoptotic proteins, including Raf kinases, BAX, BAD, NOXA, and caspase-2. (wikipedia.org)
  • Another component of the DNA repair machinery in the cell is the protein MLH1. (wikipedia.org)
  • These proteins all are regulated in the same manner and appear to differ in their sites of action within the cell. (wikipedia.org)
  • subunits
  • This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. (wikipedia.org)
  • To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special degradative tag, the ubiquitinylation. (wikipedia.org)
  • receptor
  • One function of androgen receptor that is independent of direct binding to its target DNA sequence, is facilitated by recruitment via other DNA-binding proteins. (wikipedia.org)
  • Thus
  • As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. (wikipedia.org)
  • Thus, Protein 26S proteasome non-ATPase regulatory subunit 2 (Rpn1) is an essential component of forming the base subcomplex of 19S regulatory particle. (wikipedia.org)
  • encode
  • At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4. (wikipedia.org)
  • accumulation
  • Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. (wikipedia.org)
  • Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. (wikipedia.org)
  • family
  • 14-3-3ζ is one of 7 members of the 14-3-3 protein family, which is ubiquitously expressed and highly conserved among plants and mammals. (wikipedia.org)
  • variants
  • this transcript contains an alternate open reading frame (ARF) that specifies a protein that is structurally unrelated to the products of the other variants. (wikipedia.org)
  • Alternatively spliced transcript variants encoding the same protein have been described. (wikipedia.org)
  • predominantly
  • Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. (wikipedia.org)
  • regulatory
  • The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. (wikipedia.org)
  • According to the protein interaction and topological characteristics of this multisubunit complex, the 19S regulatory particle is composed of a base and a lid subcomplex. (wikipedia.org)
  • diseases
  • Finally, we discuss miR-200c as a potential prognostic/diagnostic biomarker in several diseases, but mainly focusing on cancer and its potential application in future therapeutics. (springer.com)
  • HspB1 accumulates in protein aggregates associated with conformational diseases: Parkinson's disease (Outeiro et al. (atlasgeneticsoncology.org)
  • several
  • The p53 protein was discovered 10 years earlier by several groups, including that of David Lane and Lionel Crawford, Arnold Levine, and Lloyd Old. (wikipedia.org)