Cyclin dependent kinase inhibitor p21. Medical search. Frequent questions

Additionally, the mRNA and protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (pRb), was further down-regulated under exposure to lovastatin in condition of BRCA1 overexpression, but the expression of p21WAF1/CIP1, a cyclin-dependent kinase inhibitor (CDKI), was further up-regulated, both in vitro and in vivo detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. (nih.gov)
Our results suggest that BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway, which will provide an innovative experimental framework to study control of breast cancer cell proliferation. (nih.gov)
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)
Unlike iPS cells, undifferentiated FReP cells proliferate slowly and express low proto-oncogene c-MYC and unexpectedly high levels of cyclin-dependent kinase inhibitors p15(Ink4B) and p21(WAF1/Cip1). (ca.gov)
Remarkably, in a fashion reminiscent of quiescent stem cells, the slow replicative phenotype of undifferentiated FReP cells reverses after differentiation induction, with differentiating FReP cells proliferating faster and expressing less p15(Ink4B) and p21(WAF1/Cip1) than differentiating iPS cells. (ca.gov)
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)

PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)

In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. (lu.se)

In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.org)
Regulation of the activation of the Fanconi anemia pathway by the p21 cyclin-dependent kinase inhibitor. (uri.edu)
Additionally, ACT‑3 significantly increased autophagic cell death by inhibiting the serine‑threonine kinase/mammalian target of the rapamycin pathway. (iasp-pain.org)
Thus, the activated ERK pathway played an important role in cell cycle arrest and apoptosis via ERK‑dependent induction of p21 in MCF‑7 cells. (iasp-pain.org)
This paper focuses on our increased, though by no means complete, understanding of the vitamin-D-dependent antimicrobial pathway and attempts to adjudicate published evidence regarding the vitamin's alleged role in altering host susceptibility to infections. (hindawi.com)
DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.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)
The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy. (biomedcentral.com)
Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)

Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
D-type and E-type cyclins assemble with CDKs during the G1 phase and these holoenzymes act as rate-limiting controllers to regulate passage through the restriction point and the subsequent onset of DNA replication [ 2 , 3 ]. (biomedcentral.com)
Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
Furthermore, CDK-activating kinase (CAK) phosphorylates cyclin-bound CDKs on a single threonine residue, a modification that is essential for their activity [ 6 - 9 ]. (biomedcentral.com)
Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (nature.com)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)

We tested interactions between Drosophila cyclins and a panel of hundreds of previously identified proteins. (fhcrc.org)

In ILC and ILC-LTED cells, WNT4 led to suppression of CDKN1A/p21, which is critical for ILC cell proliferation. (nih.gov)

Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. (fhcrc.org)
A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)

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)

The cyclin-dependent kinase (Cdk) inhibitor p21Cip1 (p21) plays a crucial role in restraining cellular proliferation and maintaining cellular quiescence. (blogspot.com)

Here we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5 and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28) substrates. (nature.com)
Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)

Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. (aacrjournals.org)
It was identified that propofol inhibited the viability and invasion, but promoted apoptosis of HGC‑27 and AGS cells in a dose‑dependent manner. (spandidos-publications.com)
TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)

ILC-LTED cells remained dependent on WNT4 for proliferation, by either maintaining ER function and WNT4 regulation or uncoupling WNT4 from ER and upregulating WNT4 expression. (nih.gov)
In GC, Yang et al ( 7 ) reported that propofol suppressed the proliferation of SGC-7901 and MGC-803 cells by promoting inhibitor of growth 3 ( 7 ). (spandidos-publications.com)
In vitro, proliferation is higher in neuronal progenitor cells derived from p21-/- mice compared to cells derived from wild-type mice. (blogspot.com)
Proliferation is increased in neuronal progenitor cells after suppression of p21 using lentivirus expressing short hairpin RNA against p21. (blogspot.com)
Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)

The synthesis of another G1 phase cyclin, cyclin E, increases in late G1 and decreases once DNA replication is initiated. (biomedcentral.com)
Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
Fitness assays revealed that both women were infected with replication competent viruses, and both expressed higher mRNA levels of p21 , a host restriction factor associated with viral control. (biomedcentral.com)

Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)

Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. (frontiersin.org)

Although we did not identify any highly Clb2-specific substrates, we found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1, enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets. (nature.com)

The application of the systems biology approach to the analysis of a gene regulatory network is demonstrated with a case study of the regulation of p21 by multiple miRNAs [ 4 ]. (hindawi.com)
Concretely, E2 or BPA decreased the gene expression of p21, which is a potent cyclin-dependent kinase (Cdk) inhibitor and responsible for the cell cycle arrest at G1 phase, to proliferate the BG-1 cells. (endocrine-abstracts.org)
On the other hand, genistein upregulated the expression of p21 gene cultured in the presence of E2 or BPA, leading to the growth inhibition of the BG-1 cells. (endocrine-abstracts.org)
Also, the alteration of p21 gene expression by E2, BPA, or genistein affected the expression of its downstream genes of cell cycle, cyclin D1 and Cdk-4. (endocrine-abstracts.org)

Using in vivo and in vitro approaches the present study shows that p21 is expressed in the subgranular zone of the dentate gyrus of the hippocampus in early neuronal progenitors and in immature neurons, but not in mature neurons or astroglia. (blogspot.com)
In vivo, chronic treatment with the non-selective antidepressant imipramine as well as the norepinephrine-selective reuptake inhibitor desipramine or the serotonin-selective reuptake inhibitor fluoxetine all decrease p21 expression, and this was associated with increased neurogenesis. (blogspot.com)

Because Cdi4 was originally identified by its ability to interact with a Drosophila cyclin-dependent kinase, the finding that it interacts with cyclin E strengthened the notion that it functions in cell cycle regulation. (fhcrc.org)
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)

Taken together from these results, we may suggest an anticancer effect of genistein, a dietary phytoestrogen, on the estrogen-dependant cancers like ovarian cancer prompted by E2 or BPA. (endocrine-abstracts.org)

Treatment of Panc-1 cells with a proteasome inhibitor, MG132, increased the HPK1 protein levels in a dose-dependent manner, suggesting that alteration in proteasome activity contributes to the loss of HPK1 protein expression in pancreatic cancer. (aacrjournals.org)
Western blotting was performed to detect the protein levels of cyclin‑dependent kinase inhibitor P21 (P21), B‑cell lymphoma‑2 (Bcl‑2), matrix metalloproteinase 9 (MMP9) and E26 oncogene homolog 1 (ETS1). (spandidos-publications.com)

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 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)

p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. (lu.se)

Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)

In breast cancer patients, it is unclear whether measuring p53, mdm-2, or p21 expression provides information on how patients will respond to chemotherapy. (lu.se)
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)

p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical methods in primary tumors derived from 134 patients who took part in a randomized multicenter trial comparing docetaxel to sequential methotrexate and 5-fluorouracil (MF) in advanced breast cancer. (lu.se)
Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. (lu.se)

Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)

Targets of the cyclin-dependent kinase Cdk1. (nature.com)

Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). (biomedcentral.com)

Untreated p21-/- mice exhibit a higher degree of baseline neurogenesis and decreased immobility in the forced swim test. (blogspot.com)
Although chronic imipramine treatment increased neurogenesis and reduced immobility in the forced swim test in wild-type mice, it reduced neurogenesis and increased immobility in p21-/- mice. (blogspot.com)

We show that Cdi4 can inhibit cyclin E function both in a yeast assay and in vitro. (fhcrc.org)

We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. (hindawi.com)

Figure 2: Telomere-dependent senescence. (nature.com)

Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
Anticancer effects of the HDAC inhibitor, 3β,6β‑dihydroxyurs‑12‑en‑27‑oic acid, in MCF‑7 breast cancer cells via the inhibition of Akt/mTOR pathways. (iasp-pain.org)
ACT‑3 significantly increased the pERK1/2 and p21 in MCF‑7 cells. (iasp-pain.org)
Like the endogenous HPK1, both wild-type HPK1 and its kinase-dead mutant, HPK1-M46, overexpressed in Panc-1 cells, were also targeted by proteasome-mediated degradation. (aacrjournals.org)
Furthermore, restoring wild-type HPK1 protein in PDA cells led to the increase in p21 and p27 protein expression and cell cycle arrest. (aacrjournals.org)
Propofol could inhibit Bcl‑2 and MMP9 expression, and increase P21 expression in GC cells. (spandidos-publications.com)
Additionally, the effects of transfection with circ‑PVT1 small interfering RNA (si‑circ‑PVT1) on HGC‑27 and AGS cells could be reversed by treatment with miR‑195‑5p inhibitor. (spandidos-publications.com)

ACT‑3 significantly reduced the expression levels of cyclin D1 and cyclin‑dependent kinase 4, and upregulated the expression levels of p21 and p53. (iasp-pain.org)

According to modern concepts, inflammation plays a leading role in the genesis of almost all age-dependent diseases, which ultimately lead the body to death. (vechnayamolodost.ru)

In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. (biomedcentral.com)
These results demonstrate the unique role of p21 in the control of neurogenesis, and support the hypothesis that different classes of reuptake inhibitor-type antidepressant drugs all stimulate hippocampal neurogenesis by inhibiting p21 expression. (blogspot.com)

In light of these results, our sequence analysis revealed that Cdi4 is a unique member of the p21/p27/p57 family of Cdk inhibitors. (fhcrc.org)
Results: Data addressing the function of vectors harbouring genes specifically encoding ricin, saporin, lunasin , linamarase, and tomato thymidine kinase 1 under the control of different promoters are summarised here. (weeksmd.com)

p15, p16, p21 and p27 in mouse ovaries by immunohistochemistry to assess whether the initiation of primordial follicle growth was associated with the expression of CDKIs. (biomedcentral.com)

The anticancer activity of 3β,6β‑dihydroxyurs‑12‑en‑27‑oic acid (ACT‑3), a major component isolated from , has not yet been investigated in detail. (iasp-pain.org)
ACT‑3 inhibited total HDAC activity in a dose‑dependent manner. (iasp-pain.org)

Anatomy7

Organisms2

Chemicals and Drugs72

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes29

Disciplines and Occupations1

Information Science3

CIP17

CDKI1

WAF11

Pathway7

Tumor4

CDKs11

Proteins1

CDKN1A1

Complexes5

Tyrosine1

CDK41

P21CIP11

Specificity3

Apoptosis3

Proliferation5

Replication3

CDK21

Mammalian1

Substrates1

Gene4

Vivo2

Regulation2

Cancers1

Protein levels2

Cellular2

Progression1

Activation1

Chemotherapy3

Tumors2

Promotes1

Targets1

Overexpression1

Mice2

Yeast1

Regulatory network1

Senescence1

Cells9

Levels1

Inflammation1

Role2

Results2

Growth1

Activity2