Transcription factor cyclin dependent kinase inhibitor p21. Medical search. Frequent questions

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)
TGF-b inhibits cell growth by controlling a cytostatic program that includes activation of the cyclin-dependent kinase inhibitors p15 Ink4B and p21 WAF1/Cip1 and repression of c-myc. (tmc.edu)
Specifically, DLX4 blocked the ability of TGF-b to induce expression of p15 Ink4B and p21 WAF1/Cip1 by directly binding to Smad4 and to Sp1. (tmc.edu)
In addition, DLX4 induced expression of c-myc, a repressor of p15 Ink4B and p21 WAF1/Cip1 transcription, independently of TGF-b signaling. (tmc.edu)
The inhibitory effects of esculetin on cell viability were found to be associated with a G1 arrest in cell cycle progression that was concomitant with an inhibition of cyclin E and an induction of cyclin-dependent kinase (Cdk) inhibitor p21/WAF1/CIP1 in a p53-independent manner. (dsmc.or.kr)

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)

Several genetic alterations have been described in SCCHN, including mutations in the p53 tumor suppressor gene and mutations in genes that encode cell cycle proteins such as p16 and cyclin D1. (oncotarget.com)
The crosstalk is regulated by tumor suppressor proteins, including ARF, P21 and FBXW7, which are also frequently mutated in many cancers. (biomedcentral.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)
Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (thermofisher.com)
Cell-cycle-related proteins, such as cyclins or cyclin-dependent kinases, may have functions beyond that of cell cycle regulation. (biomedcentral.com)

Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21). (cornell.edu)
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)
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)
CDKN1A (p21) interacts with CCNE1 (cyclin E). (uth.edu)

The kinases involved are cyclin A-CDK2 at either SP190 or SP354, p38 mitogen-activated protein (MAP) kinase at SP692 in embryonic kidney cells and AKT3 at S720 in melanoma. (wikipedia.org)
Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4 kinase activities with no change in their expression. (dsmc.or.kr)
Cyclin D1, a member of the G1 cyclins, plays an important role in the G1 phase progression of the cell cycle in proliferating cells via activation of cyclin-dependent kinase 2 (CDK2), CDK4, or CDK6. (biomedcentral.com)

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)

Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. (ku.dk)
Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)

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)
Transactivation of the cyclin-dependent-kinase inhibitor p21, a downstream target of p53, and the G 1 cell cycle checkpoint were also found to be normal in the DNA-PKcs -/- MEFs. (uthscsa.edu)
Downstream targets of CDKs include transcription factor E2F and its regulator Rb. (kegg.jp)

This growth inhibition by TRO is linked to the G1 phase cell cycle arrest through the up-regulation of the cyclin-dependent kinase inhibitors p21 and p27 [ 14 - 16 ] and/or repression of cyclin D1 expression [ 17 , 18 ]. (e-roj.org)

HMGB1 can activate a series of signaling components, including mitogen-activated protein kinases (MAPKs) and AKT, which play an important role in tumor growth and inflammation, through binding to different surface receptors, such as RAGE and TLR2/4. (biomedcentral.com)
The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)

Whereas p16(INK4a) antagonizes the activities of cyclin D-dependent kinases, p19(ARF) activates the p53 transcription factor. (ku.dk)
The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). (thermofisher.com)

With aging, the cell stops dividing: it does not respond to growth factors and becomes resistant to apoptosis. (vechnayamolodost.ru)
Treating SCCHN cell lines with a pan-Aurora kinase inhibitor resulted in defective cytokinesis, polyploidy and apoptosis, which was effective irrespective of the EGFR status. (oncotarget.com)
Our results demonstrate that combined targeting of EGFR and Aurora kinases represents a therapeutic means to activate cell cycle checkpoints and apoptosis in SCCHN. (oncotarget.com)
TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. (lu.se)
Transforming growth factor β (TGFβ) is a secreted growth and differentiation factor that influences vital cellular processes like proliferation, adhesion, motility, and apoptosis. (encyclopedia.pub)
Moreover, the models also predict that mutations of RAS, ARF and P21 in the context of HMGB1 signaling can influence the cancer cell's fate - apoptosis or survival - through the crosstalk of different pathways. (biomedcentral.com)
Melatonin has oncostatic properties that are mediated by induction of apoptosis, arresting the cell cycle, regulation of metabolic activity, and the inhibition of hypoxia-inducible factor 1α (HIF-1α) activity [ 9 ]. (explorationpub.com)

The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
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)
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)
CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
Basal synaptic transmission was normal in the presence of CDK4 inhibitor. (biomedcentral.com)
however there was no significant change in paired-pulse facilitation (PPF) in slices pre-incubated with the CDK4 inhibitor from adolescent animals. (biomedcentral.com)
By the treatment of CDK4 inhibitor, the induction or the maintenance of Long-term potentiation (LTP) in response to a strong tetanus and NMDA receptor-dependent long-term depression (LTD) were normal in hippocampus. (biomedcentral.com)
However, long-term depression (LTD) induced either by group I metabotropic glutamate receptors (mGluRs) agonist or by paired-pulse low-frequency stimulation (PP-LFS) was impaired in CDK4 inhibitor pretreated slices both from neonatal and adolescent animals. (biomedcentral.com)
But the effects of the CDK4 inhibitor at slices from adolescent animals were not as robust as at slices from neonatal animals. (biomedcentral.com)
Our results indicated that the activation of cyclinD1-CDK4 is required for short-term synaptic plasticity and mGluR-dependent LTD, and suggested that this cyclin-dependent kinase may have different roles during the postnatal development in mice hippocampus area CA1. (biomedcentral.com)
This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)

These data demonstrate that the ERK pathway participates in p21 induction and subsequently leads to a decrease in the kinase activity of Cdks and inhibition of pRB phosphorylation in esculetin-mediated G1 arrest of U937 cells. (dsmc.or.kr)
Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)

VDR belongs to the superfamily of nuclear receptors for steroid hormones and regulates gene expression by acting as a ligand-activated transcription factor [ 3 ]. (biomedcentral.com)

Active TGFβ induces the heteromeric complex formation of two single transmembrane serine/threonine kinase family receptors, i.e. (encyclopedia.pub)
Phosphorylation at serine 15 of the human p53 tumor suppressor protein is induced by DNA damage and correlates with accumulation of p53 and its activation as a transcription factor. (uthscsa.edu)
The DNA-dependent protein kinase (DNA- PK) can phosphorylate serine 15 of human p53 and the homologous serine 18 of murine p53 in vitro. (uthscsa.edu)

For example, it can interact with other transcription factors such as Nkx2-5, Msx 1/2 and Sox4 to assist it binding to its target genes to regulate heart development and it can interact with histone deacetylases (HDACs) 1, 2, 3 and 5 to repress p14ARF in breast cancer and with HDAC5 to repress E-cadherin to promote metastasis in hepatocellular carcinoma. (wikipedia.org)
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)
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)
These events are dependent on the proper levels of transcription and translation of certain genes. (cancerquest.org)

During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. (oncotarget.com)

Indeed, Tbx3 binds highly conserved T-elements to activate the promoters of Eomes, T, Sox17 and Gata6, which are factors essential for mesoderm differentiation and extra embryonic endodermal. (wikipedia.org)
In this primer, we describe the key features of Hes factors and detail their roles in some representative processes of embryogenesis: namely, in the development of the nervous and digestive systems, two well-characterized processes, where Hes1 (and Hes3 and Hes5 in the nervous system) regulates cell proliferation and differentiation, and in the process of somite segmentation, where Hes7 functions as a biological clock. (biologists.com)
Both transcription factor-based reprogramming and directed differentiation approaches ultimately exploit transcription factors to influence cellular identity. (silverchair.com)
The basic helix-loop-helix transcription factor NeuroD (Neurod1) has been implicated in neuronal fate determination, differentiation and survival. (biologists.com)

New treatment protocols are aiming to reduce the dose of the multitargeted tyrosine kinase inhibitor sunitinib, as sunitinib elicits many adverse effects depending on its dosage. (bvsalud.org)

In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)

The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. (hindawi.com)

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)
It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (thermofisher.com)

DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
Here, we demonstrate that the TP53/p53-FBXO22-TFEB (transcription factor EB) axis plays an essential role in this process through upregulating basal macroautophagy/autophagy. (elsevierpure.com)

1,25(OH) 2 D 3 was as strong or stronger than Ca 2+ in its induction of the cyclin-dependent kinase inhibitors, P21 and p27. (aacrjournals.org)
Further investigation showed that inhibition of the extracellular-regulated kinase (ERK) signaling pathway reduced the induction of p21 and the inhibition of pRB phosphorylation and cyclin E expression by esculetin, which in turn overcame the G1 arrest and growth inhibition that was induced by esculetin. (dsmc.or.kr)

Combined Aurora kinase and EGFR targeting using a monoclonal anti-EGFR antibody was more effective compared to single EGFR and Aurora kinase inhibition. (oncotarget.com)
Studies with pitavastatin in primary patient derived tumor cells and established PDA lines, revealed dose dependent growth inhibition. (oncotarget.com)

Here, we discuss how transcription factors, and their unique position as the gatekeepers of cellular identity, are exploited in cell reprogramming protocols by exploring work focusing on one reprogramming paradigm - the transdifferentiation of hepatocytes to pancreatic beta cells (β-cell). (silverchair.com)
The former include hypoxia, high lactate levels or the abundance of growth factors within the cellular microenvironment. (springer.com)
Cellular aging or cellular senescence is the critical factor for the process of aging. (hindawi.com)
This receptor is found in moderate levels on some normal cells and as the gene's name implies, it is involved in cellular responses to growth factors. (cancerquest.org)

The identification of key master regulator transcription factors (which distinguish one body part from another) during embryonic development has been central in developing transdifferentiation protocols. (silverchair.com)

We also observed that down-regulation of the phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. (dsmc.or.kr)
This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)

Arrest in the G1 and G2/M phases is accompanied by elevated p53 and p21 expression. (nih.gov)
Ca 2+ strongly induced E-cadherin expression and inhibited the expression of the nuclear transcription factor, TCF4. (aacrjournals.org)
We analyzed the clinical data and performed immunohistochemistry for Epidermal growth factor receptor (EGFR) and Aurora kinase A (Aurora-A) expression in 180 SCCHN patients. (oncotarget.com)
Comparing pan-Aurora kinase and Aurora-A targeting hints towards a strong and clinically relevant biological effect mediated via Aurora kinase B. Taken together, our findings characterize a new poor risk group in SCCHN patients defined by elevated EGFR and Aurora-A protein expression. (oncotarget.com)
Ectopic expression of vector-delivered transcription factors (particularly the triumvirate of Pdx1, Ngn3 and MafA) induces reprogramming through broad transcriptional remodelling. (silverchair.com)
We examine how transdifferentiation protocols are evolving to ever more faithfully recapitulate normal developmental biology using increasingly sophisticated biomimetic techniques and ectopic transcription factor expression. (silverchair.com)
As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (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)
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)
S transition in the cell cycle, upregulated expression of tumor-promoting microenvironmental factors, and profound dysregulation of metabolic pathways (e.g., increased aerobic glycolysis, downregulation of pathways that metabolize drugs and xenobiotics). (biomedcentral.com)
It was thought to decrease the expression of a protein called mitochondrial transcription factor A (TFAM), a key player in cancer cell proliferation. (technologynetworks.com)
Finally, the expression patterns of three neuronal type-specific transcription factors, unc-3, unc-4 and unc-30 , were altered. (biologists.com)
Our data suggest that cnd-1 may specify the identity of ventral cord motor neurons both by maintaining the mitotic competence of their precursors and by modulating the expression of neuronal type-specific determination factors. (biologists.com)
The change of radiation sensitivity by combined with TRO is not dependent on the PPARγ expression level. (e-roj.org)

Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)
Cardiovascular (CV) risk factors such as hypercholesterolemia, hyperglycaemia, obesity, hypertension, smoking, and aging promote vascular inflammation and endothelial activation [ 7 - 9 ]. (hindawi.com)

TBX3 has been functionally connected to the regulation of the Wnt signalling, thereby providing a novel explanation of how signalling pathways are orchestrated by tissue-specific transcription factors. (wikipedia.org)
Peroxisome proliferator-activated receptor γ (PPARγ) is a critical transcription factor in the regulation of glucose and lipid metabolism [ 1 ]. (e-roj.org)
All of them are present in the hippocampus, where they participate in the regulation of synaptic functionality and gene transcription [ 12 - 14 ]. (biomedcentral.com)

Although highly preliminary, the findings suggest that different tumor biological factors may predict response to different chemotherapy regimens with distinct mechanisms of action. (lu.se)
The results of our phenotype analysis also indicate that it is more likely that a panel of tumor biological factors instead of only one single factor may be needed for better prediction of chemotherapy response. (lu.se)
Furthermore, senescent cells, with the secretory features known as the senescence-associated secretory phenotype (SASP), could produce proinflammatory cytokines, such as tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), and monocyte chemoattractant protein1 (MCP-1), to greatly affect the neighboring cells [ 17 , 18 ]. (hindawi.com)

Increasingly, complimentary cell culture techniques, which recapitulate the developmental microenvironment, are employed to coax cells to adopt new identities by indirectly regulating transcription factor activity via intracellular signalling pathways. (silverchair.com)
We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo . (oncotarget.com)
Transforming growth factor-beta (TGFβ) was discovered more than thirty years ago as a secreted polypeptide from sarcoma virus-infected cells that promoted the soft agar independent growth of normal rat kidney (NRK) cells [ 1 ] [ 2 ] . (encyclopedia.pub)

These modifications act in a context dependent manner to promote TBX3 protein stability, nuclear localization and transcriptional activity. (wikipedia.org)

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)
Type 1 diabetes mellitus (insulin-dependent diabetes) is characterized by hyperglycemia caused by an insulin deficiency. (researchgate.net)
In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. (researchgate.net)

Radioresistance of these tumors can be ascribed to two factors: environmental and intrinsic. (springer.com)
Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)

A better understanding of the levers governing transcription factor activity benefits our ability to generate therapeutic cell types at will. (silverchair.com)

The transcription factor encoded by the homeobox patterning gene DLX4 is overexpressed in a wide range of malignancies. (tmc.edu)

We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. (biomedcentral.com)
The life of a gene product, from transcription to degradation, is controlled by a series of regulatory decisions. (biomedcentral.com)

T-box 3 (TBX3) is a member of the T-box gene family of transcription factors which all share a highly conserved DNA binding domain known as the T-box. (wikipedia.org)

Previous reports indicate that the mechanisms of DN involve a multifactorial interaction of metabolic and hemodynamic factors such as high blood glucose, advanced glycation end-products (AGEs), and the renin-angiotensin system (RAS). (hindawi.com)

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

Transforming growth factor-b (TGF-b) is a cytokine that plays essential roles in regulating embryonic development and tissue homeostasis. (tmc.edu)

Prominent among the hits were members of the statin class of HMG-CoA reductase inhibitors, cholesterol lowering drugs that are also being evaluated in cancer. (oncotarget.com)
Excessive exposure to estrogen is a key risk factor for breast cancer [ 10 ]. (explorationpub.com)

HER2/neu (also called ERB B2 ) is the gene that encodes the human epidermal growth factor receptor type 2. (cancerquest.org)

Anatomy13

Organisms5

Diseases2

Chemicals and Drugs131

Analytical, Diagnostic and Therapeutic Techniques and Equipment17

Phenomena and Processes54

Disciplines and Occupations1

Information Science3

CIP17

WAF11

Proteins5

Cdkn1a4

Cdk23

Including D-type cyclins1

P21Cip12

Downstream3

Repression1

Protein kinases2

INK4a2

Apoptosis8

Cdk411

CDKs2

Gene expression1

Serine3

Genes4

Regulate1

Differentiation4

Tyrosine1

Activates1

Generation of reactive oxygen1

Progression2

TP532

Induction2

Inhibition2

Cellular4

Regulator1

Phosphorylation2

Expression15

Activation2

Regulation3

Tumor3

Cells3

Nuclear1

Insulin3

Tumors2

Activity1

Homeobox1

Regulatory2

Family of transcription factors1

Metabolic1

Senescence1

Embryonic development1

Cancer2

Epidermal1