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)
This protein is encoded by the CDKN1A gene located on chromosome 6 (6p21.2) in humans. (wikipedia.org)
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)
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)
The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. (cancerindex.org)
Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. (cancerindex.org)
Increasing concentrations of p53 and p21 lead to changes in protein kinase activity. (smpdb.ca)
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)
These pericryptal myofibroblasts produce the Wnt signalling ligands which bind to Frizzled receptors as well as morphogenetic protein (BMP) antagonists gremlin 1(GREM1), gremlin 2 (GREM2) on basal epithelial stem cells and also can modulate notch signaling. (biomedcentral.com)
Homeodomain-interacting protein kinase-2 (HIPK2) is a positive regulator of p53 oncosuppressor function. (aacrjournals.org)
Our data show that the stable knockdown of HIPK2 led to wtp53 misfolding, as detected by p53 immunoprecipitation with conformation-specific antibodies, and that p53 protein misfolding impaired p53 DNA binding and transcription of target genes. (aacrjournals.org)
CDK23
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)
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)
Negatively1
p21 is negatively regulated by ubiquitin ligases both over the course of the cell cycle and in response to DNA damage. (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)
Affinity2
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)
To be able stabilizing the kinetics of microtule, vincristine rapidly and reversibly bind to soluble tubulin which can increase the affinity of tublin by the induction of conformational changes of tubulin. (smpdb.ca)
Cellular2
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)
Since the early years of radiobiology the cellular effects of ionizing radiation have been studied in the context of induced chromosomal aberrations, and early models of radiation action were largely based upon such studies (Savage 1996). (nationalacademies.org)
Replication2
The ability of p21 to inhibit apoptosis in response to replication fork stress has also been reported. (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)
Transcription3
These events are dependent on the proper levels of transcription and translation of certain genes. (cancerquest.org)
We present evidence that zinc supplementation to HIPK2i cells increased p53 reactivity to conformation-sensitive PAb1620 (wild-type conformation) antibody and restored p53 sequence-specific DNA binding in vivo and transcription of target genes in response to Adriamycin treatment. (aacrjournals.org)
Epigenetic alterations comprising local and global changes in DNA and histone modifications, transcription factor binding, disorganization of the nuclear lamina, and misfolding of the genome are hallmarks of aging. (oaepublish.com)
However p21 may inhibit apoptosis and does not induce cell death on its own. (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)
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)
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)
Region1
Vincristine binds to β-tubulin subunits at the positive end of microtubules at a region called the _Vinca_-binding domain. (smpdb.ca)
Cells2
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)
Despite factors in codon, all apoptotic dwarfism genes person three employed cells( CRs) and each is with RAS and MEK synapses, although with pulmonary cyclins. (evakoch.com)
Complex1
Specifically, over the G1/S transition it has been demonstrated that the E3 ubiquitin ligase complex SCFSkp2 induces degradation of p21. (wikipedia.org)
Rate2
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)
Binding between vincristine and solubale tubulin decreases the rate of microtubule dynamics (lengthening and shortening) and increases the duration of attenuated state of microtubules. (smpdb.ca)
Domain1
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)
Phase1
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)