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  • 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)
  • p21 was simultaneously identified as WAF1 (Wild-type p53-Activated Fragment1) and as CIP1 (Cyclin-dependent kinase Inhibitor Protein), suggesting a direct link between p53 , negative regulation of the kinases required for G1-S transition and therefore G1 arrest. (celldeath.de)
  • 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)
  • 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)
  • Inactivation of PARP during the execution phase of apoptosis by caspase cleavage might be necessary to prevent NAD+ and ATP depletion and thus to prevent a switch from an ATP-dependent apoptotic mode of cell death to an energy depletion-induced necrotic mode (Amours et al, 2001, J. Cell Science, 114(20) 3771-77). (celldeath.de)
  • 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)
  • mitogen-activa
  • It was further shown that cGMP, p42/p44 mitogen-activated protein kinase, or AKT kinase-mediated signaling pathways did not contribute to the YC-1-induced effect. (aspetjournals.org)
  • SM22α arrested cell cycle progression through segregation of Ras with Raf-1 and downregulation of the Raf-1-MEK1/2-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling cascade. (ahajournals.org)
  • 3 As one of the best-characterized signaling events downstream of Ras, the mitogen-activated protein kinase (MAPK) cascade that sequentially involves Ras, Raf, MEK1/2, and the extracellular signal-regulated kinase (ERK) 1/2 MAPK is activated in response to a multitude of mitogenic stimuli. (ahajournals.org)
  • Extracellular Signal
  • 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)
  • mouse embryonic fibroblasts
  • Using chromatin immuno-precipitation and high throughput sequencing (ChIP-Seq), we performed a genome-wide mapping of NFI DNA binding sites in primary mouse embryonic fibroblasts. (biomedcentral.com)
  • CUL4A deletion results in delayed S phase entry in mouse embryonic fibroblasts, which is rescued by deletion of p21. (wikipedia.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)
  • 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)
  • PCNA binds to flap endonuclease 1 (FEN-1), a structure-specific endonuclease involved in DNA replication. (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)
  • 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)
  • inhibit
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)

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  • apoptosis
  • Smads2/3/4 increased, but Smad7 decreased, MPK38-mediated apoptosis signal-regulating kinase-1 (ASK1)/transforming growth factor-β (TGF-β)/p53 signaling. (deepdyve.com)
  • Introduction cell proliferation, differentiation, apoptosis, migration, The identification of a growing list of intracellular extracellular matrix remodeling, immune functions, and kinases that phosphorylate Smad proteins suggests that tumor metastasis. (deepdyve.com)
  • Cell Death and Disease (2018) 9:471 Page 2 of 13 apoptosis signal-regulating kinase-1 (ASK1), and murine molecular mechanisms involved in the regulation of meta- protein serine-threonine kinase 38 (MPK38)/maternal bolic homeostasis by TGF-β signaling remain poorly 1,7,8 embryonic leucine zipper kinase (MELK) , suggesting understood. (deepdyve.com)
  • We demonstrated that CP-31398 induced p53-dependent apoptosis and G2 arrest, as well as p53-independent Gl arrest. (ubc.ca)
  • Since CP-31398 was shown to be able to rescue mutant p53 functions, we treated melanoma cells with CP-31398 together with the topoisomerase I inhibitor camptothecin which was shown to induce p53-dependent apoptosis, to determine if CP-31398 would enhance melanoma chemosensitivity. (ubc.ca)
  • Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. (hindawi.com)
  • Recent reports have indicated that terpinen-4-ol exerts its antitumor effects by triggering caspase-dependent apoptosis in human melanoma cells or by inducing necrotic cell death and cell-cycle arrest in mouse mesothelioma and melanoma cell lines without affecting normal cells [ 14 , 15 ]. (hindawi.com)
  • 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)
  • serine
  • PAK1 is one of six members of the PAK family of serine/threonine kinases which are broadly divided into group I (PAK1, PAK2 and PAK3) and group II (PAK4, PAK6 and PAK5/7). (wikipedia.org)
  • interacts
  • 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)
  • 1995
  • The human PAK1 was identified as a GTP-dependent interacting partner of Rac1 or Cdc42 in the cytosolic fraction from neutrophils, and its complementary DNA was cloned from a human placenta library by Martin and Colleagues in 1995. (wikipedia.org)
  • embryonic
  • Studies of human embryonic stem cells (hESCs) commonly report the nonfunctional p53-p21 axis of the G1/S checkpoint pathway, and its relevance for cell cycle regulation and the DNA damage response (DDR). (wikipedia.org)
  • MAPK
  • These findings are discussed in relation to the role of SPRY1 as an inhibitor of ERK/MAPK signaling and to a possible explanation of its effect on cell proliferation. (biomedcentral.com)
  • Essential to most RTK-mediated signaling is the activation of the extracellular-signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling cascade. (biomedcentral.com)
  • MAPK, CDK or GSK3) signalling and consequently regulates cell proliferation (in part through control of cyclin D1 levels and stability) and cell survival. (wikipedia.org)
  • complex
  • Neph-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity. (uni-koeln.de)
  • Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. (genecards.org)
  • 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)
  • 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)
  • Skp2 is the substrate recruiting component of the SCFSkp2 complex, which targets cell cycle control elements, such as p27 and p21. (wikipedia.org)
  • This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). (wikipedia.org)
  • regulate
  • PAK1-signaling dependent cellular functions regulate both physiologic and disease processes, including cancer, as PAK1 is widely overexpressed and hyperstimulated in human cancer, at-large. (wikipedia.org)
  • primarily
  • 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)
  • conformational
  • Upon binding, several events occur, such as overall conformational changes of receptors, receptor dimerization, nuclear translocation, and binding to specific estrogen response elements (ERE) on DNA. (frontiersin.org)
  • The nature of the bound nucleotide and the ensuing conformational modification of the Switch domains dictates the ability of RhoA to bind or not to partner proteins (see below). (wikipedia.org)
  • PAK1 activators relieve this autoinhibition and initiate conformational rearrangements and autoPhosphorylation events leading to kinase activation. (wikipedia.org)
  • After binding the Cyclin in the PSTAIRE helix, the protein changes its conformational structure to expose the phosphorylation motif. (wikipedia.org)
  • effector
  • Knockdown of FUBP1 or expression of a dominant-negative FUBP1 (DNA-binding domain lacking effector activity) led to proliferation arrest in U2OS and Saos-2 osteosarcoma cells due to reduced c-myc expression (He et al. (atlasgeneticsoncology.org)
  • Furthermore
  • Furthermore, over- on the activity of these interacting kinases in order to expression of Smads2/3/4 improves, whereas Smad7 decipher the molecular interplay between TGF-β and overexpression worsens, obesity-associated metabolic other intracellular signaling pathways. (deepdyve.com)
  • cleavage
  • Increased sub-G1 population and annexin-V binding, activation of caspases 9 and 3, cleavage of poly(ADPribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated involvement of the mitochondrial apoptotic pathway in terpinen-4-ol-treated A549 and CL1-0 cells. (hindawi.com)
  • metabolic
  • Effect of metabolic inhibitors on the cytotoxicity of MSE and MIT in metabolically competent MCL-5 cells Discussion Genotoxic potential of MSE and MIT Introduction Materials and methods 3. (kratomextractworld.com)
  • It will address molecular problem on the students of metabolic Ibé, stellar inhibitors and clear Euclidean decisions from all over the attention. (ecombinatii.ro)
  • inactive
  • Group I PAKs exist in an inactive, closed homodimer conformation wherein AID of one molecule binds to the kinase domain of another molecule, and activated in both GTPase-dependent and -independent manners. (wikipedia.org)
  • activity
  • parameters by differentially regulating MPK38 activity in MPK38/MELK, an AMP‐activated protein kinase HFD-induced obese mice. (deepdyve.com)
  • Upon induction of differentiation in leukemia cells (HL-60 and U937), binding activity of FUBP1 to the c-myc promoter is lost. (atlasgeneticsoncology.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)
  • These effects were rescued with reintroduction of p21 and p27, but not reintroduction of cyclin D1 suggesting that CIP/KIP proteins are crucial for cyclin D-CDK activity. (wikipedia.org)
  • There are additional functions of CDK6 not associated with its kinase activity. (wikipedia.org)
  • Cdc25
  • Previously, we showed that Notch signaling is required for the mitotic-to-endocycle transition, through downregulating String/Cdc25, and Dacapo/p21 and upregulating Fizzy-related/Cdh1. (biomedcentral.com)
  • The precise effects of Pin1 depend upon the system: Pin1 accelerates dephosphorylation of Cdc25 and Tau, but protects phosphorylated cyclin D from ubiquitination and proteolysis. (wikipedia.org)
  • Nuclear
  • Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export. (genecards.org)
  • This occurs when p27 is phosphorylated on Ser(10) which allows for CRM1, a nuclear export carrier protein, to bind to and remove p27 from the nucleus. (wikipedia.org)
  • pathways
  • Smads2/3/4 stimulate MPK38- dependent ASK1/TGF-β/p53 signaling pathways, whereas have focused on the regulatory role of Smad phosphor- ylation in the TGF-β signaling pathway. (deepdyve.com)
  • PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response. (uni-koeln.de)
  • Both NAD-dependent and Pttg1-dependent pathways were responsible for mediating different subsets of these alterations, also incorporating changes in VCP/p97 localization and Ube1 expression. (biomedcentral.com)