• WAF1
  • Białko p21 (WAF1) jest w stanie oddziaływać z jądrowym antygenem komórek proliferujących ( proliferating cell nuclear antigen − PCNA), czynnikiem dodatkowym polimerazy DNA , i tym samym odgrywać rolę regulatora zarówno przy replikacji materiału genetycznego w fazie S jak i przy naprawie łańcucha . (wikipedia.org)
  • identified a protein p21 (WAF1) which was present in cells expressing wild type p53 but not those with mutant p53, moreover constitutive expression of p21 led to cell cycle arrest in a number of cell types. (wikipedia.org)
  • 4,5 ERK1/2 signaling is also necessary for the degradation or downregulation of cyclin- dependent kinase (CDK) inhibitors, such as p21 waf1 (p21) and particularly p27 kip1 (p27), thereby eliminating their growth-suppressive activities. (ahajournals.org)
  • Liver mRNA levels of transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF)-β, cyclin-dependent kinase inhibitor p27 kip (p27), and cyclin-dependent kinase inhibitor p21 WAF1/CIP1 (p21) were quantified by real-time polymerase chain reaction. (aspetjournals.org)
  • apoptosis
  • Rodriguez R, Meuth M. Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress . (wikipedia.org)
  • However p21 may inhibit apoptosis and does not induce cell death on its own. (wikipedia.org)
  • The ability of p21 to inihbit apoptosis in response to replication fork stress has also been reported. (wikipedia.org)
  • p57 can bind JNK1/SAPK, a stress-related kinase, and block its activity, protecting against JNK1-regulated apoptosis. (wikipedia.org)
  • Besides that, dysregulated cyclin E activity causes cell lineage-specific abnormalities, such as impaired maturation due to increased cell proliferation and apoptosis or senescence. (wikipedia.org)
  • In human retinal pigment eptithelial cells, loss of Cdt2 expression also result in p21 dependent delayed S-phase entry, and re-expression of p21 in S-phase, which results cycles of incomplete replication, long term accumulation of p21, and in some cases induction of apoptosis. (wikipedia.org)
  • proliferating cell nu
  • p21 interacts with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. (wikipedia.org)
  • The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21. (genesilico.pl)
  • The conserved FEN-1 C terminus binds proliferating cell nuclear antigen (PCNA) and positions FEN-1 to act primarily as an exonuclease in DNA replication, in contrast to its endonuclease activity in DNA repair. (sdbonline.org)
  • inhibits
  • Conclusion- These findings suggest that high expression of SM22α inhibits cell proliferation via reduction of the response to mitogen stimuli in VSMCs and provide a novel mechanism by which VSMCs maintain their contractile phenotype and resist mitogenic stimuli in an SM22α-dependent manner. (ahajournals.org)
  • A PCNA binding peptide from p21Cip1 competes with Fen1 peptides for binding to PCNA, disrupts the Fen1-PCNA complex in replicating cell extracts, and concomitantly inhibits DNA synthesis. (sdbonline.org)
  • Cdk1
  • Recent studies have shown that the cyclin A2-CDK1 complex triggers cyclin B1-CDK1 activation which results in chromatin condensation and the breakdown of the nuclear envelope. (wikipedia.org)
  • substrate
  • May bind an additional third magnesium ion after substrate binding. (genesilico.pl)
  • Essential amino acids for substrate binding and catalysis of human flap endonuclease 1. (genesilico.pl)
  • The crystal structure of Pyrococcus furiosus FEN-1, active-site metal ions, and mutational information indicate interactions for the single- and double-stranded portions of the flap DNA substrate and identify an unusual DNA-binding motif. (sdbonline.org)
  • flap
  • PCNA binds to flap endonuclease 1 (FEN-1), a structure-specific endonuclease involved in DNA replication. (sdbonline.org)
  • replication
  • Studies have also demonstrated that the E3 ubiquitin ligase complex CRL4Cdt2 degrades p21 in a PCNA dependent manner over S-phase, necessary to prevent p21 dependent re-replication, as well as in response to UV irradiation. (wikipedia.org)
  • Competition between homologous regions of Fen1 and p21Cip1 for binding to the same site on PCNA may provide a mechanism to co-ordinate the functions of PCNA in DNA replication and repair (Warbrick, 1997). (sdbonline.org)
  • FEN-1 mutations altering PCNA binding should reduce activity during replication, likely causing DNA repeat expansions as seen in some cancers and genetic diseases (Hosfield, 1998). (sdbonline.org)
  • CRL4Cdt2 also degrades PCNA-bound PR-Set7/SET8, which is a histone 4 methyltransferase, and the p12 subunit of DNA polymerase δ, which is crucial for DNA replication. (wikipedia.org)
  • cancers
  • This has resulted in the conclusion that most, if not all, cancers exhibit one or more cell cycle defects ( Sherr, 1996 ), and that effective cancer therapy will require restoring normal cell cycle control. (aspetjournals.org)
  • Dysregulation of cyclin E occurs in 18-22% of the breast cancers. (wikipedia.org)
  • novel
  • A brief overview of results obtained with ATP-competitive inhibitors such as palbociclib and dinaciclib is presented, followed by a compilation of new avenues that have been pursued toward the development of novel, non-ATP-competitive CDK inhibitors. (aspetjournals.org)
  • extracellular
  • The infection of rat carotid arteries with recombinant adenovirus encoding SM22α inhibited neointimal hyperplasia via suppression of the Raf-1-MEK1/2-extracellular signal-regulated kinase 1/2 signaling pathway. (ahajournals.org)
  • In contrast, the growth response of decorin-overexpressing ASMCs to TGF-β1, as well as the expression of TGF-β1-responsive genes, such as plasminogen activator inhibitor-1 and versican (an extracellular matrix proteoglycan), was diminished. (ahajournals.org)
  • complex
  • Specifically it contains a Cy1 motif in the N-terminal half, and weaker Cy2 motif in the C-terminal domain that allow it to bind CDK in a region that blocks its ability to complex with cyclins and thus prevent CDK activation. (wikipedia.org)
  • Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
  • The enzyme's active-site structure suggests that DNA binding induces FEN-1 to clamp onto the cleavage junction to form the productive complex. (sdbonline.org)
  • It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, and is essential[citation needed] for the G1/S transition. (wikipedia.org)
  • The smaller subunit of this Damaged DNA Binding protein complex is known as DDB2 and is able to directly bind DNA lesions associated with UV-irradiation. (wikipedia.org)
  • This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). (wikipedia.org)
  • tumor
  • Favorable results with palbociclib and its recent U.S. Food and Drug Administration approval demonstrate that CDK inhibitors with narrow selectivity profiles can have clinical utility for therapy based on individual tumor genetics. (aspetjournals.org)
  • Cyclin E is a prognostic marker in breast cancer, its altered expression increased with the increasing stage and grade of the tumor. (wikipedia.org)
  • Fen1
  • FEN1 is an essential enzyme in an inaccurate pathway for repair of double-strand breaks in DNA called microhomology-dependent alternative end joining or microhomology-mediated end joining (MMEJ). (wikipedia.org)
  • Deletion analysis suggests that p21Cip1 and Fen1 bind to the same region of PCNA. (sdbonline.org)
  • PCNA
  • Can bind simultaneously to both PCNA and EP300. (genesilico.pl)
  • Acetylation also reduces DNA-binding activity but does not affect interaction with PCNA or EP300. (genesilico.pl)
  • this region contains an 8 amino acid conserved PCNA-binding motif. (sdbonline.org)
  • This motif shares critical residues with the PCNA-binding region of p21Cip1. (sdbonline.org)
  • A 28-amino acid region of human FEN-1 (residues 328-355) and a 29-amino acid region of human XPG (residues 981-1009) contain the PCNA binding activities. (sdbonline.org)
  • all three compete with one another for binding to PCNA. (sdbonline.org)
  • A conserved arginine in FEN-1 (Arg339) and XPG (Arg992) was found to be crucial for PCNA binding activity. (sdbonline.org)
  • human
  • This study was undertaken to characterize the antiangiogenic properties of a series of original dual thromboxane A(2) (TXA(2)) inhibitors derived from torasemide, a marketed loop diuretic with TXA(2) antagonistic properties, by evaluating their effects on human endothelial cell migration, adhesion, and viability in vitro, as well as in the ex vivo rat aortic ring assay. (ac.be)
  • Moreover, both quiescent and activated human satellite cells can be identified by the membrane-bound neural cell adhesion molecule (N-CAM/CD56/Leu-19), a cell-surface glycoprotein. (wikipedia.org)
  • cell
  • Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang X-M, Leferovich J, Cheverud JM, Lieberman P, Heber-Katz E. Lack of p21 expression links cell cycle control and appendage regeneration in mice . (wikipedia.org)
  • p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. (wikipedia.org)
  • Recent work exploring p21 activation in response to DNA damage at a single-cell level have demonstrated that pulsatile p53 activity leads to subsequent pulses of p21, and that the strength of p21 activation is cell cycle phase dependent. (wikipedia.org)
  • In this cell type, p53 activates numerous microRNAs (like miR-302a, miR-302b, miR-302c, and miR-302d) that directly inhibit the p21 expression in hESCs. (wikipedia.org)
  • p21 is negatively regulated by ubiquitin ligases both over the course of the cell cycle and in response to DNA damage. (wikipedia.org)
  • CDK protein levels remain stable, whereas cyclin levels vary in a way that periodically activates CDK during the cell cycle ( Pines, 1991 ). (aspetjournals.org)
  • Cyclin A1 was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of meiosis. (wikipedia.org)
  • These dual TXA(2) inhibitors dose dependently inhibited endothelial cell migration in chemotaxis assays using vascular endothelial growth factor ( VEGF) as a chemoattractant but failed to affect cell adhesion and viability. (ac.be)
  • These data suggest that our original dual TXA(2) inhibitors bear antiangiogenic properties, mainly by inhibiting endothelial cell migration. (ac.be)
  • 15 16 The growth-inhibitory effect of decorin in malignant cell lines involves an increase in the cyclin kinase inhibitor p21. (ahajournals.org)
  • Cyclin E overexpression can lead to G1 shortening, decrease in cell size or loss of serum requirement for proliferation. (wikipedia.org)
  • Impact of cyclin E overexpression on Smad3 activity in breast cancer cell lines. (wikipedia.org)
  • It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle. (wikipedia.org)