Proteins 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)
Primary mouse embryo fibroblasts lacking Cip1 and Kip1 genes encoding inhibitors of cyclin-dependent kinase-2 were used to further explore the effects of oncogenic Ras on arrest of the cell division cycle. (ku.dk)
Although early passage primary fibroblast strains that lack both p21(Cip1) and p27(Kip1) fail to assemble cyclin D-dependent kinases, oncogenic Ras retained its ability to induce p19(ARF), but not p16(INK4a), protecting Cip/Kip-null cells from proliferating and undergoing transformation. (ku.dk)
Therefore, in the absence of p16(INK4a), p21(Cip1), and p27(Kip1), oncogenic Ras affects the functions of genes required for completion of the cell cycle. (ku.dk)
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)
We demonstrated that deferasirox increased expression of the metastasis suppressor protein N-myc downstream-regulated gene 1 and upregulated the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) while decreasing cyclin D1 levels. (birmingham.ac.uk)
As a universal inhibitor of cyclin-dependent kinases and one of the target genes of the tumor suppresser p53, p21Waf1/Cip1 can act as a tumor suppresser through its ability to control cell cycle progression. (ox.ac.uk)
To study the function of p21Waf1/Cip1 protein and to investigate its tissue distribution, a panel of anti-p21Waf1/Cip1 monoclonal antibodies was generated. (ox.ac.uk)
These anti-p21Waf1/Cip1 monoclonal antibodies were initially raised against a GST-p21Waf1/Cip1 fusion protein produced in bacteria. (ox.ac.uk)
Finally, epitope mapping of the anti-p21Waf1/Cip1 antibodies using a peptide library covering the entire p21Waf1/Cip1 protein sequence indicates that two of the antibodies recognize a region of p21Waf1/Cip1 close to that bound by proliferating cell nuclear antigen. (ox.ac.uk)
HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip). (cret-signal.com)

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)

This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. (wikipedia.org)
However p21 may inhibit apoptosis and does not induce cell death on its own. (wikipedia.org)
The ability of p21 to inhibit apoptosis in response to replication fork stress has also been reported. (wikipedia.org)
Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. (aacrjournals.org)
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)
Our results indicated that terpinen-4-ol induced apoptosis through a mitochondria-mediated pathway in NSCLC cells and that the apoptosis elicited by terpinen-4-ol was p53 dependent. (hindawi.com)
Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
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)
LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. (lsbio.com)
A key feature of prostate cancer progression is the induction and activation of survival proteins, including the Inhibitor of Apoptosis (IAP) family member survivin. (oncotarget.com)
As a potassium-specific ionophore, beauvericin A increases intracellular calcium concentrations and triggers DNA fragmentation and apoptosis through a calcium dependent caspase 3-sensitive pathway. (medindex.am)
TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
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)
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)

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)
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)

Specifically, over the G1/S transition it has been demonstrated that the E3 ubiquitin ligase complex SCFSkp2 induces degradation of p21. (wikipedia.org)
A rise in the levels of the p53 protein induces the expression of p21 cyclin-dependent kinase inhibitor. (reactome.org)
Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. (ku.dk)
Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. (lsbio.com)
Our study demonstrates that survivin and APE1/Ref-1 are significantly higher in human prostate cancer specimens compared to noncancerous controls and that APE1/Ref-1 redox-specific inhibition with small molecule inhibitor, APX3330 and a second-generation inhibitor, APX2009, decreases prostate cancer cell proliferation and induces cell cycle arrest. (oncotarget.com)
Treatment with the stress agent prostaglandin A 2 (PGA 2 ) induces expression of the cyclin-dependent kinase inhibitor p21. (johnshopkins.edu)

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)
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)
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 p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (prospecbio.com)
Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. (fhcrc.org)
Interestingly, although inhibition of the ERK pathway did not prevent the PGA 2 -triggered increase in cytoplasmic HuR, it did impair the formation of endogenous and in vitro [HuR-p21 mRNA] complexes and further prevented the PGA 2 -mediated stabilization of the p21 mRNA, suggesting that ERK-mediated events were required for binding HuR to the p21 mRNA and preventing its decay. (johnshopkins.edu)
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)
Cyclin E forms complexes during this interval with CDK2. (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)

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

UBE3A is associated with cervical cancer and may combine with the E6 proto-oncogene encoded by HPV16 within cervical cancer cells to form the E6/E6-AP protein complex through the ubiquitin proteasome pathway ( 4 ). (spandidos-publications.com)
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)

Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (prospecbio.com)
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (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)
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)

Whereas p16(INK4a) antagonizes the activities of cyclin D-dependent kinases, p19(ARF) activates the p53 transcription factor. (ku.dk)

Tumor suppressor genes encode proteins that normally provide negative control of cell proliferation. (medscape.com)
One of the activated genes is an inhibitor of cyclin-dependent kinases. (lsbio.com)
Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.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)
Studies of human genome demonstrate that protein-coding genes only occupy less than 2% of the entire genome [ 1 ]. (ijbs.com)
This results in inhibition of NFκB activity and the NFκB-dependent expression of anti-apoptotic genes of the Bcl-2 family [ 15 ]. (biomedcentral.com)
structural genes encode proteins that are not involved in gene regulation. (cret-signal.com)
As a result of this differential cell cycle-regulatory gene expression by HDAC inhibition, the retinoblastoma protein retains a transcriptional repression of its downstream target genes required for S phase entry. (cret-signal.com)

Synchronous neurotransmission is triggered when Ca(2+) binds to synaptotagmin 1 (Syt1), a synaptic-vesicle protein that interacts with SNAREs and membranes. (cret-signal.com)

Estrogen receptor-alpha (ERalpha) promotes proliferation of breast cancer cells, whereas tumor suppressor protein p53 impedes proliferation of cells with genomic damage. (nih.gov)
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)
PTEN encodes a protein kinase of the same name and functions as a tumor suppressor through regulation of cell proliferation. (medscape.com)
Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)
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)
The mechanisms underlying this reduction of SMC proliferation by HDAC inhibition involve a growth arrest in the G(1) phase of the cell cycle that is due to BVD-523 cost an inhibition of retinoblastoma protein phosphorylation. (cret-signal.com)

We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
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)
Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors. (rcsb.org)
The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)

Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. (reactome.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)
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)
The synthesis of another G1 phase cyclin, cyclin E, increases in late G1 and decreases once DNA replication is initiated. (biomedcentral.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)
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)

We found that loss of HPK1 protein expression correlated significantly with the progression of pancreatic intraepithelial neoplasias ( P = 0.001) and development of invasive PDA. (aacrjournals.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)
Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. (lsbio.com)

Inhibition of APE1/Ref-1 redox function significantly reduced NFĸB transcriptional activity, survivin mRNA and survivin protein levels. (oncotarget.com)
Here, we present evidence that p21 expression increases through PGA 2 -triggered stabilization of the p21 mRNA and further show that these events require the mitogen-activated protein (MAP) kinase ERK. (johnshopkins.edu)
Binding experiments using either endogenous p21 mRNA or in vitro-labeled p21 transcripts revealed a specific PGA 2 -dependent association of the p21 mRNA with the RNA-binding protein HuR. (johnshopkins.edu)
RNA interference-based knockdown of HuR abundance further served to demonstrate the contribution of HuR-mediated p21 mRNA stabilization toward enhancing p21 expression after PGA 2 treatment. (johnshopkins.edu)
Collectively, our results indicate that PGA 2 stabilizes the p21 mRNA through an ERK-independent increase in cytoplasmic HuR levels and an ERK-dependent association of HuR with the p21 mRNA. (johnshopkins.edu)
Additionally, circRNAs modulate pre-mRNA alternative splicing and possess protein-coding capacity. (ijbs.com)
Application of unidirectional pulsatile shear stress to human umbilical vein endothelial cells (HUVECs) decreased PDCD4 protein but not mRNA level. (plos.org)
Specifically, the PDCD4 protein combines directly with the mRNA coding region of the target gene ( MYB/c-MYB ) to block translation [2] . (plos.org)
cyclin D1 mRNA expression and cyclin D1 promoter activity. (cret-signal.com)

TP53 encodes the protein p53, which is known as the "guardian of the genome. (medscape.com)
In response to DNA double strand breaks, serine at position 15 of the TP53 (p53) tumor suppressor protein is rapidly phosphorylated by the ATM kinase. (reactome.org)
For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)

Low expression of CDK6 protein in ZR-75-1, Neuro-2a, and INS-1 cells is consistent with the predicted expression pattern. (cellsignal.com)
Immunoprecipitation of CDK6 protein from Jurkat cell extracts. (cellsignal.com)

Due to the role of oncogenic transcriptional activators NFĸB and STAT3 in survivin protein expression, and APE1/Ref-1 redox activity regulating their transcriptional activity, we assessed selective inhibition of APE1/Ref-1's redox function as a novel method to halt prostate cancer cell growth and survival. (oncotarget.com)
Finally, we provide evidence that these observations are applicable in vivo by demonstrating that HDAC inhibition decreased neointima formation and expression of cyclin D1 in a murine model of vascular injury. (cret-signal.com)

The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.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)
The HIV-1 Vpu protein is an oligomeric integral membrane protein essential for particle release, viral load and CD4 degradation. (biomedcentral.com)
The stable association of Vpu with βTrCP also affects the latter's cellular functions, one of which is to direct the proteosomal degradation of inhibitor of kappa B (IκB) [ 14 ]. (biomedcentral.com)

This locus, however, also encodes a protein from an alternative reading frame, designated p19ARF. (medscape.com)

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

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)

Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. (hindawi.com)
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)

Ionizing radiation together with ERalpha knock down results in additive effect on transcription of endogenous p53-target gene p21 (CDKN1) in human breast cancer cells. (nih.gov)

We report here a technique using a single molecule, recombinant human fibromodulin protein (FMOD), to reprogram human fibroblasts into multipotent cells. (ca.gov)

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)
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)
They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)

Cellular identity is determined by the transcriptional profile which comprises the subset of mRNAs, and therefore proteins, being expressed by a cell at a given point in time. (silverchair.com)

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)
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)
After MG132 withdrawal, wild-type HPK1 protein expression was markedly decreased within 24 hours, but kinase-dead HPK1 mutant protein expression was sustained for up to 96 hours. (aacrjournals.org)
The overexpression of miRNA‑375 significantly suppressed the levels of protein expression of ubiquitin‑protein ligase E3A (UBE3A) and Insulin‑like growth factor‑1 receptor (IGF‑1R) in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
Propofol could inhibit Bcl‑2 and MMP9 expression, and increase P21 expression in GC cells. (spandidos-publications.com)
Meanwhile, miR‑195‑5p inhibitor reversed the si‑circ‑PVT1‑induced low expression of ETS1. (spandidos-publications.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)
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)
Scope includes mutations and abnormal protein expression. (cancerindex.org)
Whether Vpu is a viral pathogenesis factor remains to be established, but compared to HIV-1, closely related retroviruses such as HIV-2 and SIV that lack expression of a fully functional Vpu protein also cause less severe disease outcomes. (biomedcentral.com)
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)
Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.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)

[ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)

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)

Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein that is essential in activating oncogenic transcription factors. (oncotarget.com)

Likewise, p16/p21 double knockout mice, which have very few senescent cells, showed similar delays in wound closure. (jax.org)

However, both Mabs were also found to induce complement-dependent cytotoxicity (CDC) reaction for lysis of cancer cells, an immune property which is not shared by peptide analogs of GnRH. (annexpublishers.co)

p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. (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 first described CID systems involve microbe-derived dimerizing ligands, such as rapamycin, that direct protein neo-associations that rewire eukaryotic cell signaling 5 . (nature.com)
Similarly, HPK1 protein was not expressed in any of eight PDA cell lines examined but was expressed in immortalized human pancreatic duct epithelial (HPDE) cells. (aacrjournals.org)
The eukaryotic cell cycle is controlled by a network of interacting regulatory proteins. (fhcrc.org)
Overall, single protein, FMOD-based, cell reprograming bypasses the risks of mutation, gene instability, and malignancy associated with genetically-modified iPS cells, and provides an alternative strategy for engineering patient-specific multipotent cells for basic research and therapeutic application. (ca.gov)

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)

We will discuss three key proteins that function as tumor suppressors implicated in the development of pediatric (and some adult) cancers: pRB, p53, and PTEN. (medscape.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)

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)

CDKIs are capable of suppressing growth, and several lines of evidence strongly suggest that at least some CDKIs may be tumor suppressor proteins. (prospecbio.com)

Anatomy7

Organisms2

Chemicals and Drugs72

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes29

Disciplines and Occupations1

Information Science3

CIP112

Levels of cyclin‑depe1

Apoptosis15

WAF12

Induces6

Complexes9

CDKN1A1

Proto-oncogene2

CDKs9

INK4A1

Genes8

Binds1

Proliferation6

CDK44

Phosphorylation1

Replication3

Synthesis3

Progression3

MRNA9

TP535

CDK62

Inhibition2

Pathway1

Degradation3

Encodes a protein1

Ubiquitin ligases1

Interacts1

Survivin2

Endogenous1

Fibroblasts1

Activation4

Cellular1

Expression14

Retinoblastoma1

Downstream1

Effector1

Senescent cells1

Induce1

Cell6

CDK22

Cancers1

PCNA1

Rapamycin1

CDKIs1