Cdk6 gene cyclin dependent kinase inhibitor p27. Medical search. Frequent questions

Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. (wikipedia.org)
In mice and humans, two more cyclin D proteins have been identified. (wikipedia.org)
Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.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)
Analysis of G(1) regulatory proteins demonstrated that protein levels of CDK2, CDK4, cyclin D1, and cyclin A were decreased in a time-dependent manner, but not those of CDK6 and cyclin E, by EB1089. (drlauda.at)

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)

The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. (biomedcentral.com)
Palbociclib instead primarily targeted monomeric CDK4 and CDK6 (CDK4/6) in breast tumor cells. (rcsb.org)

Rb reduces its binding to E2F and thereby allows E2F-mediated activation of the transcription of cyclin E and cyclin A, which bind to Cdk1 and Cdk2 respectively to create complexes that continue with Rb phosphorylation. (wikipedia.org)
Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
Cyclin-dependent kinase 3 (CDK3) is a major player driving retinoblastoma (Rb) phosphorylation during the G0/G1 transition and in the early G1 phase of the cell cycle, preceding the effects of CDK4/cyclin D, CDK6/cyclin D, and CDK2/cyclin E. CDK3 can also directly regulate the activity of E2 factor (E2F) by skipping the role of Rb in late G1, potentially via the phosphorylation of the E2F1 partner DP1. (bvsalud.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)

CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
Here, we review new progress in the control of cyclin D-dependent cancer cell cycle and proliferation, along with identification of novel E3 ligase for the stability of cyclin D. Cullin4-RING E3 ligase (CRL4)AMBRA1 complex plays a critical role in regulating D-type cyclins through their protein destabilization to control S phase entry and maintain genomic integrity. (bvsalud.org)

ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
The CDK4/Cyclin D complex is also negatively regulated by p21/CIP1/CDKN1A and p27/Kip1. (rndsystems.com)
Phospho-p27 Kip1 (Thr198) Antibody detects endogenous levels of p27 Kip1 only when phosphorylated at Threonine 198. (affbiotech.cn)

Cyclin A and E dependent kinase complexes also function to inhibit the E3 ubiquitin ligase APC/C activating subunit Cdh1 through phosphorylation, which stabilizes substrates such as cyclin A. The coordinated activation of this sequence of interrelated positive feedback loops through cyclins and cyclin dependent kinases drives commitment to cell division to and past the G1/S checkpoint. (wikipedia.org)
The retinoblastoma protein (RB1), a regulator of cell proliferation, is functionally inactivated in HCC by CYCLIN D/E-mediated phosphorylation. (bvsalud.org)
Mechanistically, FOXM1 binds RB1 and DNMT3B to repress the expression of FOXO1, leading to a decrease in the levels of the CDK-inhibitors, creating an environment for phosphorylation and inactivation of RB1. (bvsalud.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)
This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)
Activation of CDK4 requires binding of a D-type Cyclin and phosphorylation of Thr172 by the CAK kinase complex. (rndsystems.com)

The CDKN2A/B locus contains genes encoding cell cycle inhibitors, including p16 Ink4a , which have not yet been implicated in the control of hepatic glucose homeostasis. (diabetesjournals.org)

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)
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 abundance of cyclins is generally regulated by protein synthesis and degradation through APC/C- and CRL-dependent pathways. (wikipedia.org)
One of the members of the pathways, MAPK activates a transcription factor Myc, which alters transcription of genes important in cell cycle, among which is cyclin D. In this way, cyclin D is synthesized as long as the growth factor is present. (wikipedia.org)
Random set analysis was used to identify biological pathways enriched for genes differentially regulated in tumors (compared with 59 samples of normal mucosa). (biomedcentral.com)
What pathways are this gene/protein implicaed in? (cancerindex.org)
The recent findings advance our knowledge for the prevention of the premature activation of the major oncogenic pathways including MYC and the cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6) axis. (bvsalud.org)
According to weighted gene co-expression network analysis, pathways positively related to adipogenic differentiation are significantly activated at the differentiation stage, while WNT, FOXO and other pathways that inhibit preadipocyte differentiation are negatively regulated. (biomedcentral.com)
Calcium mineral stations are essential mediators of several varied procedures c-Kit-IN-2 such as for example hormone and neurotransmitter launch, activation of intracellular signalling pathways, pacemaker adjustments or activity in gene manifestation. (cell-signaling-pathways.com)

Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (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)
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)

Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A. In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21CIP1/WAF1 and p16INK4a which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D. Cyclin D possesses a tertiary structure similar to other cyclins called the cyclin fold. (wikipedia.org)
miR-128-5p targets the tissue inhibitor of metalloproteinases (TIMPs), silent information regulator 2 (SIRT2), peroxisome proliferator-activated receptor (PPAR), and p21 genes, which are linked to the behaviours of VSMCs. (hindawi.com)

from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin. (lookformedical.com)
This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. (affbiotech.cn)
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. (cancerindex.org)

An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. (childrensmercy.org)

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)
Here, we show that p16 Ink4a deficiency enhances fasting-induced hepatic glucose production in vivo by increasing the expression of key gluconeogenic genes. (diabetesjournals.org)

The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. (wikipedia.org)
The synthesis of another G1 phase cyclin, cyclin E, increases in late G1 and decreases once DNA replication is initiated. (biomedcentral.com)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. (lookformedical.com)

For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
However, the mechanism of RB1-inactivation is unclear because only small percentages of HCCs exhibit amplification of CYCLIN D/E or mutations in the CDK-inhibitory genes. (bvsalud.org)

Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. (wikipedia.org)
In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle progression. (wikipedia.org)
Namely, cyclin D-Cdk4/6 complex partially phosphorylates retinoblastoma tumor suppressor protein (Rb), whose inhibition can induce expression of some genes (for example: cyclin E) important for S phase progression. (wikipedia.org)
Rb is an important regulator of genes responsible for progression through the cell cycle, in particular through G1/S phase. (wikipedia.org)
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)
Therefore, the activation of the cyclin D-CDK4/6 axis stimulates cell proliferation and cancer progression, which represents a unique therapeutic target. (bvsalud.org)
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)

Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the cell cycle. (wikipedia.org)

p21 and other tumor suppressor genes' inactivation are therefore most likely involved in the first steps of the cancer model, with later stages possibly involving protooncogene activation and inflammation. (medscape.com)

The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)

In general, all stages of the cell cycle are chronologically separated in humans and are triggered by cyclin-Cdk complexes which are periodically expressed and partially redundant in function. (wikipedia.org)
Cyclin D levels in proliferating cells are sustained as long as the growth factors are present, a key player for G1/S transition is active cyclin D-Cdk4/6 complexes. (wikipedia.org)
The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
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)

Moreover, as the level of PD-L1 is considered in the severe clinical problem in the patients treated with CDK4 inhibitors, we assume that a therapeutic combination using PD-L1 immunotherapy might lower the development of drug resistance and targeting cyclin D will likely inhibit tumor growth and overcome resistance to cyclin D-associated CDK4/6 inhibitors. (bvsalud.org)

AA and the extracellular regulated protein kinase 1/2 (ERK1/2) blocker U0126 markedly inhibited migration, elevated smooth muscle 22 α (SM22 α ) expression, repressed VSMC proliferation, elevated miR-466f-3p and miR-425-3p expression, and suppressed miR-27a-5p and miR-128-5p expression in ox-LDL-induced VSMCs. (hindawi.com)
The migration, phenotypic transformation, and proliferation of VSMCs lead to vascular wall remodeling, which is mediated by activation of extracellular regulated protein kinases 1/2 (ERK1/2) signalling [ 9 ]. (hindawi.com)
Several studies have shown that miRNAs play multiple roles in the phenotypic transformation, migration, and proliferation of VSMCs by inhibiting ERK1/2 activation [ 11 , 12 ], partly by regulating the tissue inhibitor of metalloproteinases (TIMPs)-MMPs and p21-cyclins interactions [ 13 - 18 ]. (hindawi.com)

[ 1 ] Identifying candidate precursors or enabling genes may pave the way for cancer screening, as with the ret proto-oncogene and medullary thyroid carcinoma . (medscape.com)

However, we have shown that inhibition of CDK4/6 upregulates protein levels of RB1 and CDK6 for acquisition of drug resistance to CDK4/6 inhibitors. (bvsalud.org)

miR-128-5p directly targeted the 3′UTR-binding sequences of the p21 gene, negatively regulated p21 expression, and supported the proliferation of VSMCs. (hindawi.com)

Since RA signalling is highly dose-dependent, a fine-tuning regulatory mechanism is required. (mdpi.com)

One of the best known substrates of cyclin D/Cdk4 and -6 is the retinoblastoma tumor suppressor protein (Rb). (wikipedia.org)

Further evaluation of this role has been hampered by the lack of selective pharmacological inhibitors. (bvsalud.org)
Virk-Baker et al 2010) For example the combination of a natural VEGF inhibitor along with lower doses of a pharmacological agent may prove helpful in reducing the unwanted side effects of chemotherapy. (compassionateacupuncture.com)

VSMCs were transfected with the miR-128-5p mimic and inhibitor, and the migration, phenotypic modulation, and proliferation of VSMCs were investigated. (hindawi.com)
The miR-128-5p mimic promoted the migration and proliferation of VSMCs and suppressed p21, p27, and SM22ɑ expression. (hindawi.com)
The inhibitor increased p21, p27, and SM22ɑ expression and repressed the migration, phenotypic transformation, and proliferation of VSMCs. (hindawi.com)
Our research showed that the migration, phenotypic transformation, and proliferation of ox-LDL-induced VSMCs were repressed by AA through inhibiting miR-128-5p by targeting the p21 gene, which may provide an effective option for the treatment of atherosclerosis. (hindawi.com)
A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. (cancerindex.org)
EB1089 inhibited the proliferation of NCI-H929 cells and RPMI8226 cells in a dose-dependent manner among three myeloma cell lines tested. (drlauda.at)
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)

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)
Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)

We also summarize the strategy for inhibition of the cyclin D-associated kinases CDK4/6 and other potential cell cycle regulators for targeting cancer with altered cyclin D expression. (bvsalud.org)
Circular RNAs (circRNAs) are a new member of noncoding RNAs (ncRNAs) that have recently been described as key regulators of gene expression. (biomedcentral.com)

The first five-helix bundle is a conserved cyclin box, a region of about 100 amino acid residues on all cyclins, which is needed for Cdk binding and activation. (wikipedia.org)
However, it is composed of different amino acid residues as the same patch in cyclins E, A, and B. Growth factors stimulate the Ras/Raf/ERK that induce cyclin D production. (wikipedia.org)
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)

Cyclin D has no effect on G1/S transition unless it forms a complex with Cdk 4 or 6. (wikipedia.org)
We were also able to pinpoint specific changes within each gene set that seem to play key roles at each transition. (biomedcentral.com)

D-type cyclins are frequently deregulated in human cancer and promote cell division in part through activation of CDK4/6. (bvsalud.org)
Under some circumstances, p27 is associated with active CDK4, but no mechanism for activation has been described. (rcsb.org)

MicroRNAs (miRNAs) are small noncoding sequences involved in the negative regulation of gene expression. (hindawi.com)

One model proposes that cyclin D quantities, and thus cyclin D- Cdk4 and -6 activity, gradually increases during G1 rather than oscillating in a set pattern as do S and M cyclins. (wikipedia.org)
This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
Importantly, BCRC-3 could directly interact with miR-182-5p, and subsequently act as a miRNA sponge to promote the miR-182-5p-targeted 3'UTR activity of p27. (biomedcentral.com)

We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)

PMID: 10102234 [PubMed - indexed for MEDLINE] 1: Exp Cell Res 2000 Feb 1;254(2):279-86 Cell cycle arrest induced by the vitamin D(3) analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27. (drlauda.at)

In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. (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)

Altered expression of this gene has been observed in multiple human cancers. (cancerindex.org)
The expression of this gene is regulated by interferon-gamma and lipopolysaccharide. (cancerindex.org)

The yeast homologue of cyclin D, referred to as CLN3, interacts with Cdc28 (cell division control protein) during G1. (wikipedia.org)
This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. (thermofisher.com)

Anatomy8

Organisms2

Chemicals and Drugs75

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes29

Disciplines and Occupations1

Information Science3

Proteins5

Including D-type cyclins1

CDK4 and CDK62

Cdk26

Control of cyclin2

Kip13

Phosphorylation6

CDKN2A1

CDKI2

Pathways7

Cdks7

Targets2

Encodes3

INK41

INK4a2

Synthesis3

Mutations2

Progression7

Binds1

Tumor suppr1

Serine1

Complexes4

Inhibit1

ERK13

Oncogene1

Protein levels1

Negatively regulated1

Regulatory1

Substrates1

Pharmacological2

Proliferation7

Senescence2

Regulators2

Amino acid3

Transition2

Activation2

Regulation of gene ex1

Activity3

Complex1

Induction1

Dose-dependent1

Phase1

Expression of this gene2

Cdc282