Cdkn1a cyclin dependent kinase inhibitor p21. Medical search. Frequent questions

The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, and thus functions as a regulator of cell cycle progression at G1 and S phase. (wikipedia.org)
This gene encodes the cyclin-dependent kinase inhibitor p21(WAF1/Cip1), a factor implicated in cell cycle, senescence, and cancer. (ed.ac.uk)
This new and unprecedented evidence for a link between SdhD dysfunction and p21(WAF1/Cip1) will open new avenues for the study of the mechanisms that cause tumors in Sdh mutants. (ed.ac.uk)
Protein levels of CDKN1A -encoded p21 CIP1/WAF1 were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-of-function approach. (biomedcentral.com)
Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 in a p53-dependent manner. (biomedcentral.com)
SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)
The CDK4/Cyclin D complex is also negatively regulated by p21/CIP1/CDKN1A and p27/Kip1. (rndsystems.com)

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)

p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated with inhibition of CDK2. (wikipedia.org)
Experiments looking at CDK2 activity within single cells have also shown p21 to be responsible for a bifurcation in CDK2 activity following mitosis, cells with high p21 enter a G0/quiescent state, whilst those with low p21 continue to proliferate. (wikipedia.org)
Follow up work, found evidence that this bistability is underpinned by double negative feedback between p21 and CDK2, where CDK2 inhibits p21 activity via ubiquitin ligase activity. (wikipedia.org)
also found that γ-irradiation of fibroblasts induced a p53 and p21 dependent cell cycle arrest, here p21 was found bound to inactive cyclin E/CDK2 complexes. (wikipedia.org)
The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (affbiotech.cn)
Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. (affbiotech.cn)
Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. (affbiotech.cn)
The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). (novusbio.com)

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)
E2f1 mice manifest impaired GC responses, which is rescued by restoring EZH2 expression, thus defining a positive feedback loop in which EZH2 controls GC B cell proliferation by suppressing CDKN1A, enabling cell cycle progression with a concomitant phosphorylation of Rb and release of E2F1.The histone methyltransferase EZH2 silences genes by generating H3K27me3 marks. (cornell.edu)
At the molecular level, pitavastatin induced expression of the cyclin dependent kinase (CDK) inhibitor p21 in a cholesterol independent manner, blocked repressive phosphorylation of the Retinoblastoma tumor suppressor protein at CDK targeted sites, and reduced expression of E2F target genes required for progression through the G1/S boundary. (oncotarget.com)
Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. (rcsb.org)
Activation of CDK4 requires binding of a D-type Cyclin and phosphorylation of Thr172 by the CAK kinase complex. (rndsystems.com)
Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. (nih.gov)

SMRT knockdown decreased the activity of two p53-dependent reporter genes as well as the expression of p53 target genes, such as CDKN1A (which encodes p21). (nih.gov)
This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. (affbiotech.cn)
This gene encodes a potent cyclin-dependent kinase inhibitor. (nih.gov)

We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors. (rcsb.org)
Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. (affbiotech.cn)
Cyclin-dependent Kinase 4 (CDK4) is a 303 amino acid (aa) member of the Ser/Thr kinase family with a predicted molecular weight of 33.7 kDa. (rndsystems.com)
CDK4 may be useful as a prognostic marker for hepatocellular carcinoma and its kinase activity has been reported to promote the progression of T cell acute lymphoblastic leukemia. (rndsystems.com)
Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. (nih.gov)
At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. (nih.gov)
This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)

Cytoplasmic p21 expression can be significantly correlated with lymph node metastasis, distant metastases, advanced TNM stage (a classification of cancer staging that stands for: tumor size, describing nearby lymph nodes, and distant metastasis), depth of invasion and OS (overall survival rate). (wikipedia.org)
Studies with pitavastatin in primary patient derived tumor cells and established PDA lines, revealed dose dependent growth inhibition. (oncotarget.com)
The Notch signaling network exerts oncogenic and tumor‑suppressive effects in a cancer stage‑ or (sub)type‑dependent manner. (spandidos-publications.com)
Vinca alkaloids are also thought to increase apoptosis by increasing concentrations of p53 (cellular tumor antigen p53) and p21 (cyclin-dependent kinase inhibitor 1) and by inhibiting Bcl-2 activity. (smpdb.ca)

The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. (nih.gov)

p21 is negatively regulated by ubiquitin ligases both over the course of the cell cycle and in response to DNA damage. (wikipedia.org)

Collectively, these data highlight a biological role for SMRT in mediating DNA damage responses and suggest a model where p53 binding to the DAD limits HDAC3 interaction with this coregulator, thereby facilitating SMRT coactivation of p53-dependent gene expression. (nih.gov)

hCDC4 interacts with cyclin E. This interaction was modelled on a demonstrated interaction between human CDC4 and cyclin E from an unspecified species. (uth.edu)

To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. (hindawi.com)
Finally, the integration of quantitative data and modeling helped us to generate and validate hypotheses about mechanisms of collective miRNA repression on p21. (hindawi.com)
Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21). (cornell.edu)

Rather, p53 accumulation by either knockdown of Mdm2 or addition of an Mdm2 inhibitor, Nutlin-3, before irradiation strongly attenuated the UV-induced DDR and increased cell survival. (rupress.org)
The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. (ox.ac.uk)

The mechanism of OGF-OGFr action on DNA synthesis was related to the cyclin-dependent kinase inhibitory pathway because knockdown of p16 or p21 in OVCAR-3 cells, and p21 in SKOV-3 cells, eliminated OGF's inhibitory effect on growth. (nih.gov)

This protein is encoded by the CDKN1A gene located on chromosome 6 (6p21.2) in humans. (wikipedia.org)

In this model, the senescence-sensitive promoter from the cyclin-dependent kinase inhibitor 2A ( Cdkn2a ) gene, also known as p16 INK4a , drives expression of 3MR, a fusion protein that is composed of luciferase and red fluorescent protein (RFP) reporters and herpes simplex virus-1 thymidine kinase, which converts ganciclovir (GCV) into an apoptosis inducer. (jax.org)

GC B cells of Cdkn1a Ezh2 mice have high levels of phospho-Rb, indicating that loss of Cdkn1a enables progression of cell cycle. (cornell.edu)
This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. (cancerindex.org)

p21 is a potent cyclin-dependent kinase inhibitor (CKI). (wikipedia.org)

The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.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 through the cell cycle. (novusbio.com)

Exogenous OGF was observed to have a dose-dependent, serum-independent, reversible, and receptor-mediated inhibitory action on cell proliferation that was dependent on RNA and protein synthesis. (nih.gov)
Small-molecule inhibitors, antagonistic monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bispecific antibodies or biologics (bsAbs) and chimeric antigen receptor-modified T cells (CAR-Ts) targeting Notch signaling components have been developed as investigational anti-cancer drugs ( 10 - 12 ). (spandidos-publications.com)

p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. (wikipedia.org)
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)
However p21 may inhibit apoptosis and does not induce cell death on its own. (wikipedia.org)
Studies of p53 dependent cell cycle arrest in response to DNA damage identified p21 as the primary mediator of downstream 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)
Recent work has now found that in human cell lines SCFSkp2 degrades p21 towards the end of G1 phase, allowing cells to exit a quiescent state, whilst CRL4Cdt2 acts to degrade p21 at a much higher rate than SCFSkp2 over the G1/S transition and subsequently maintain low levels of p21 throughout S-phase. (wikipedia.org)
The maintenance of nucleus pulposus (NP) cell and intervertebral disc integrity benefits largely from well-controlled mitochondrial quality, surveilled by mitochondrial dynamics (fission and fusion) and mitophagy, but the outcome is cellular context-dependent that remain to be clarified. (bvsalud.org)
Description: A sandwich ELISA for quantitative measurement of Human Cyclin dependent kinase inhibitor 3(CDKN3) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. (jemsec.com)
Additionally, forced expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a G1 cell cycle arrest and CDKN1A upregulation. (biomedcentral.com)
However, CDKN1A upregulation by NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts cell-specific effects. (biomedcentral.com)
Using a 3D B cell follicular organoid system that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S phase transition of GC B cells in a Cdkn1a-dependent manner. (cornell.edu)
Here the authors use a 3D GC organoid and show EZH2 mediates germinal centre (GC) formation through epigenetic silencing of CDKN1A and release of cell cycle checkpoints. (cornell.edu)
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
The cell division process is dependent on a tightly controlled sequence of events. (cancerquest.org)
The outcome of this decision-making process is cell state dependent and, consequently, requires the integration of vast amounts of information that is encoded in the local abundance and functional state of a multitude of biomolecules acting as cell state sensors and transmitters. (biomedcentral.com)
Loss of hematopoietic stem cell function was associated with decreased expression of Cdkn1a (encoding the cell cycle inhibitor p21(cdk)), Sfpi1, Hoxb4 and Bmi1 (encoding the transcription factors PU.1, HoxB4 and Bmi-1, respectively) and altered integrin expression in Lin(-)Sca-1(+)c-Kit(+) cells, whereas PU.1 was upregulated in erythroid progenitors. (ox.ac.uk)
Immunocytochemistry/ Immunofluorescence: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on HeLa cell. (novusbio.com)

Network pharmacology analysis and bioinformatics analysis showed that PTGS2, JUN, MYC, and CDKN1A might be crucial target genes in the primary mechanism of SQP in treating NASH and improving the inflammatory response. (hindawi.com)

p21 interacts with cyclin E. (uth.edu)

Canonical Notch signaling activates the transcription of BMI1 proto‑oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context‑dependent manner, while non‑canonical Notch signaling activates NF‑κB and Rac family small GTPase 1. (spandidos-publications.com)

SMRT bound directly to p53 and was recruited to p53 binding sites within the p21 promoter. (nih.gov)

Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts. (hindawi.com)
The results of WB and qRT-PCR showed that the expression of PTGS2, JUN, MYC, and CDKN1A was higher in NASH rats than in normal rats and decreased after SQP treatment. (hindawi.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)
Western Blot: Cyclin H Antibody (1B8) [H00000902-M01] - CCNH monoclonal antibody (M01), clone 1B8 Analysis of CCNH expression in HeLa. (novusbio.com)
Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (novusbio.com)

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These events are dependent on the proper levels of transcription and translation of certain genes. (cancerquest.org)

Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden. (ox.ac.uk)

Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in Tissue homogenates and other biological fluids. (jemsec.com)
Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs. (spandidos-publications.com)
Immunohistochemistry-Paraffin: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on formalin-fixed paraffin-embedded human testis. (novusbio.com)
Sandwich ELISA: Cyclin H Antibody (1B8) [H00000902-M01] - Detection limit for recombinant GST tagged CCNH is approximately 1ng/ml as a capture antibody. (novusbio.com)

Specifically, p21 has a high affinity for the PIP-box binding region on PCNA, binding of p21 to this region is proposed to block the binding of processivity factors necessary for PCNA dependent S-phase DNA synthesis, but not PCNA dependent nucleotide excision repair (NER). (wikipedia.org)
As such, p21 acts as an effective inhibitor of S-phase DNA synthesis though permits NER, leading to the proposal that p21 acts to preferentially select polymerase processivity factors depending on the context of DNA synthesis. (wikipedia.org)

Specifically, over the G1/S transition it has been demonstrated that the E3 ubiquitin ligase complex SCFSkp2 induces degradation of p21. (wikipedia.org)

The ability of p21 to inhibit apoptosis in response to replication fork stress has also been reported. (wikipedia.org)

The binding of p21 to CDK complexes occurs through p21's N-terminal domain, which is homologous to the other CIP/KIP CDK inhibitors p27 and p57. (wikipedia.org)
This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (novusbio.com)

Working in mouse models, it was also shown that whilst mice lacking p21 were healthy, spontaneous tumours developed and G1 checkpoint control was compromised in cells derived from these mice. (wikipedia.org)

OBJECTIVE: This paper aimed to assess the clinical efficacy, adverse reactions, and safety of employing PD-1 inhibitors in conjunction with chemotherapy as a treatment strategy for advanced gastric cancer (GC). (bvsalud.org)
CONCLUSION: PD-1 inhibitor combined with chemotherapy was more effective when treating patients with advanced GC. (bvsalud.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)

The silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is an established histone deacetylase 3 (HDAC3)-dependent transcriptional corepressor. (nih.gov)
Depletion of GPS2 and TBL1, components of the SMRT corepressor complex, but not histone deacetylase 3 (HDAC3) decreased p21-luciferase activity. (nih.gov)

The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)
Increasing concentrations of p53 and p21 lead to changes in protein kinase activity. (smpdb.ca)

Description: A sandwich quantitative ELISA assay kit for detection of Human Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in samples from tissue homogenates or other biological fluids. (jemsec.com)

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)
This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. (novusbio.com)

Deletion of Cdkn1a rescues the GC reaction in Ezh2 mice. (cornell.edu)
Likewise, p16/p21 double knockout mice, which have very few senescent cells, showed similar delays in wound closure. (jax.org)

Anatomy7

Organisms2

Chemicals and Drugs70

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes30

Disciplines and Occupations1

Information Science3

CIP17

WAF11

CDK28

Phosphorylation6

Encodes3

CDK48

Tumor4

Inhibits1

Negatively regulated1

Gene expression1

Interaction1

Repression3

Mdm22

Knockdown1

Humans1

INK4a1

Progression2

Potent1

Protein encoded by this gene2

Receptor2

Cell18

Target genes1

Interacts1

BHLH1

Promoter1

Expression5

Genes2

Somatic1

Antibody4

Synthesis2

Degradation1

Apoptosis1

Complexes2

Checkpoint1

Chemotherapy2

Activation1

Histone2

Activity2

Biological1

Complex2

Mice2