CDK4 and CDK6InhibitorKinaseInhibitsVitroCyclinsMonoclonal AntibodyTumor suppressorInducesOverexpressionInhibitorsAntibodyGeneCDK2KnockoutCDK1DifferentiationRecombinantApoptosisPotentCatalyticIsotypeJurkatProteinsSerineGlioblastomaRabbitEnzymePrimary microcephalyLymphomasExpressionStemPROTACKinasesSequenceTargetsCancerSquamous cell carcOntologyAstrocytesFibroblastsPhosphorylationPeripheralNeutrophilsMCPHRolesRegulators
CDK4 and CDK612
- Inhibitors of the cyclin-dependent kinases CDK4 and CDK6 induce cell-cycle arrest in RB1-proficient tumors and have had promising results in several tumor types. (aacrjournals.org)
- The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. (prospecbio.com)
- p15 INK4b and p16 INK4a are closely related proteins and both act on the Rb-pathway through the inhibition of the proliferation-promoting cyclin-dependent kinases CDK4 and CDK6. (biomedcentral.com)
- Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. (neobiotechnologies.com)
- Serine/Threonine Kinases (STKs), Cyclin-dependent protein kinase 4 (CDK4) and CDK6-like subfamily, catalytic (c) domain. (umbc.edu)
- CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. (umbc.edu)
- CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. (umbc.edu)
- CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. (umbc.edu)
- Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. (umbc.edu)
- The 113insArg mutant p16(INK4a) was unable to bind cdk4 and cdk6 in an in vitro binding assay. (lu.se)
- The p16(INK4A) protein attaches (binds) to two other proteins called CDK4 and CDK6. (medlineplus.gov)
- CDK4 and CDK6 normally stimulate the cell to continue through the cycle and divide. (medlineplus.gov)
Inhibitor4
- For example, CDK6 is involved in the differentiation of T cells, acting as an inhibitor of differentiation. (wikipedia.org)
- Based on a database search, we identified abemaciclib, an FDA-approved Cdk4/Cdk6 inhibitor used for the treatment of metastatic breast cancer, as potent inhibitor of HIPK2, HIPK3, and DYRK1A. (nature.com)
- In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O 6 -benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-βRI inhibitor) seeking to overcome GB treatment resistance. (nih.gov)
- It is a specific inhibitor of cdk4/cdk6, and a tumor suppressor involved in the pathogenesis of a variety of malignancies. (neobiotechnologies.com)
Kinase8
- Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. (wikipedia.org)
- This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor Retinoblastoma protein making CDK6 an important protein in cancer development. (wikipedia.org)
- There are additional functions of CDK6 not associated with its kinase activity. (wikipedia.org)
- 6-phosphofructokinase (PFK1) and pyruvate kinase M2 (PKM2), enzymes that catalyze irreversible, rate-limiting steps in glycolysis, were directly phosphorylated and inhibited by cyclin D3-CDK6, suggesting that cyclin D3-CDK6 may have a unique role in glucose metabolism. (aacrjournals.org)
- The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. (aacrjournals.org)
- We determined the crystal structures of HIPK3 and DYRK1A bound to abemaciclib, showing a similar binding mode to the hinge region of the kinase as observed for Cdk6. (nature.com)
- The drug candidate acts by targeting cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6). (pharmaceutical-technology.com)
- The protein interaction landscape of the human CMGC kinase group. (nature.com)
Inhibits1
- Cyclin D3-CDK6 inhibits the glycolytic enzymes PFK1 and PKM2 to prevent T-ALL cell apoptosis. (aacrjournals.org)
Vitro2
- Remarkably, DYRK1A is inhibited by abemaciclib to the same extent as Cdk4/Cdk6 in vitro, raising the question of whether targeting of DYRK1A contributes to the transcriptional inhibition and therapeutic activity of abemaciclib. (nature.com)
- To validate these findings in vitro, we showed that CAF-cocultured CRC cells expressed an increased expression of GSK3β, β-catenin, CDK6, and NF-κB. (tmu.edu.tw)
Cyclins2
- In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. (wikipedia.org)
- For instance, overexpression of cyclins or the elimination of CDK inhibitors or pRB due to genetic mutation are common cause in human cancer. (ukessays.com)
Monoclonal Antibody1
- Formalin-fixed, paraffin-embedded human cervix stained with P16INK4aRecombinant Rabbit Monoclonal Antibody (CDKN2A/4844R). (neobiotechnologies.com)
Tumor suppressor2
- Conclusions: Pharmacological intervention with gMG suppressed CRC carcinogenesis and stemness via downregulating GSK3/β-catenin/CDK6 and upregulating the miR-26b-5p tumor suppressor. (tmu.edu.tw)
- Recently, reduced expression of CDK10 has been observed in several cancerous human tissue, suggesting that CDK10 is a tumor suppressor gene. (jcancer.org)
Induces2
- However, in T-cell acute lymphoblastic leukemia (T-ALL), which predominately expresses CDK6 and the activating cyclin, cyclin D3, inhibition of CDK6 or cyclin D3 induces apoptosis. (aacrjournals.org)
- CP-10 induces nearly 72% degradation of CDK6 at 10 nM and 89% at 100 nM in human glioblastoma U251 cells. (xcessbio.com)
Overexpression8
- This pathway is a known route altered in cancer cells, when there is an aberrant overexpression of CDK6 and CDK4. (wikipedia.org)
- 1 Chromosomal translocation leading to overexpression of the CDK6 gene, which is located in 7q21, has recently been described in splenic marginal zone lymphoma (SMZL). (ashpublications.org)
- Overexpression of CDK6 is considered to contribute to leukemogenesis through dysregulation of cell proliferation, thereby favoring progression through the G1 phase. (ashpublications.org)
- It seems likely that CDK6 overexpression is implicated in lymphomas with low proliferative index and, as we show here, may also be involved in other low-grade malignancies such as B-cell chronic lymphocytic leukemia (B-CLL). (ashpublications.org)
- Marked overexpression of CDK6 was observed in all 3 patients with CDK6 rearrangement compared with normal peripheral blood lymphocytes and with B-CLL without CDK6 involvement ( Figure 1 ). (ashpublications.org)
- As previously reported, 2 CDK6 overexpression can result from aberrant variable-diversity-joining (VDJ) or variable-joining (VJ) recombination, leading to the juxtaposition of the CDK6 gene with the Ig gene enhancer during B-cell differentiation. (ashpublications.org)
- Overexpression of CDK6. (ashpublications.org)
- Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. (platcovid.com)
Inhibitors2
- High levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors in multiple tumor types. (aacrjournals.org)
- Together, these findings elucidate a prosurvival role for cyclin D3-CDK6 in metabolism, in addition to its role in cell-cycle progression, and suggest that high levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors. (aacrjournals.org)
Antibody4
- Description: A polyclonal antibody for detection of Met from Human, Mouse, Rat. (davincieuropeanbiobank.org)
- Description: A Rabbit Polyclonal antibody against CDKN3 from Human/Mouse. (bioworldantibodies.com)
- Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human Cdkn3 - N-terminal region. (bioworldantibodies.com)
- Human-specific nestin antibody was used to verify the identity of tumor cells. (nrtisinhibitor.com)
Gene8
- Altered expression of this gene has been observed in multiple human cancers. (cancerindex.org)
- The CDK6 gene is conserved in eukaryotes, including the budding yeast and the nematode Caenorhabditis elegans. (wikipedia.org)
- The CDK6 gene is located on chromosome 7 in humans. (wikipedia.org)
- To analyze CDK6 involvement in B-CLL, we have examined the status of the CDK6 gene in bone marrow or blood samples from a further 8 adult patients with B-CLL carrying cytogenetic abnormalities (deletions, duplications, or translocations) involving bands 7q21 to 7q22 (1.5% of our B-CLL series). (ashpublications.org)
- In 3 patients, involvement of the CDK6 gene was found by at least 2 different methods. (ashpublications.org)
- FISH and Southern blot analysis showed that an interesting common feature was that in all 3 cases the CDK6 gene was rearranged by reciprocal translocations involving either Ig κ, Ig λ, or IgH locus and not with only the Ig κ light chain locus as has previously been reported in other series. (ashpublications.org)
- In addition, our findings demonstrate the involvement of the CDK6 gene in B-CLL, underlying that those abnormalities are not restricted to SMZL. (ashpublications.org)
- Recent analyses of the p16INK4a gene revealed homozygous deletions, nonsense, missense, or frameshift mutations in several human cancers. (neobiotechnologies.com)
CDK21
- However, in recent years, new evidence proved that the presence of CDK6 is not essential for proliferation in every cell type, the cell cycle has a complex circuitry of regulation and the role of CDK6 might be more important in certain cell types than in others, where CDK4 or CDK2 can act as protein kinases compensating its role. (wikipedia.org)
Knockout1
- In mutant Knockout mice of CDK6, the hematopoietic function is impaired, regardless of otherwise organism normal development. (wikipedia.org)
CDK11
- Recently, a series of studies revealed the diagnostic and prognostic value of CDKs (mainly CDK1-7) in different types of human cancer, including oral cancer, medulloblastoma, pancreatic cancer ( 11 - 14 ). (jcancer.org)
Differentiation4
- Even though CDK6 and CDK4 share 71% amino acid identity, this role in differentiation is unique to CDK6. (wikipedia.org)
- In this study, we investigated how higher-order chromatin structure modulates differential expression of the human INK4b-ARF-INK4a locus during progenitor cell differentiation, cellular ageing and senescence of cancer cells. (biomedcentral.com)
- Developmentally regulated EZH2 levels are one of the factors that can determine the higher order chromatin structure and expression pattern of the INK4b-ARF-INK4a locus, coupling human progenitor cell differentiation to proliferation control. (biomedcentral.com)
- CDK6 plays an important role in cell differentiation. (umbc.edu)
Recombinant1
- CDKN2A Human Recombinant produced in E.Coli, it's a single non-glycosylated polypeptide chain containing 156 amino acids, approximately 16.5 kDa. (prospecbio.com)
Apoptosis4
- For example, CDK6 plays a role in the accumulation of the apoptosis proteins p53 and p130, this accumulation keeps cells from entering cell division if there is DNA damage, activating pro- apoptotic pathways. (wikipedia.org)
- In vivo , palbociclib induced apoptosis of human T-ALL cells, but did not induce apoptosis in T-ALL cells expressing phosphomimetic PFK1 and PKM2 mutants. (aacrjournals.org)
- Moreover, in breast cancer cells, which express CDK4 instead of CDK6, palbociclib induced cell-cycle arrest instead of apoptosis, further indicating that expression of cyclin D3 and CDK6 in T-ALL cells promotes apoptosis in response to palbociclib. (aacrjournals.org)
- Additionally, 16 of 18 nonleukemic cancer cell lines exhibiting high expression of cyclin D3 and CDK6 underwent apoptosis in response to palbociclib, and, in melanoma patient-derived xenografts, high cyclin D3 and CDK6 expression was associated with tumor regression after CDK4/6 inhibition. (aacrjournals.org)
Potent1
- Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders. (xcessbio.com)
Catalytic1
- The CDK6 protein contains a catalytic core composed of a serine/threonine domain. (wikipedia.org)
Isotype1
- Lane 1 is 10% input, lane 2 is Rabbit (DA1E) mAb IgG XP ® Isotype Control #3900, and lane 3 is CDK6 (E3E3Q) Rabbit mAb. (cellsignal.com)
Jurkat1
- Immunoprecipitation of CDK6 protein from Jurkat cell extracts. (cellsignal.com)
Proteins2
- A) Organization of the human INK4b-ARF-INK4a locus (not drawn to scale), encoding three distinct proteins, p15 INK4b , p14 ARF and p16 INK4a . (biomedcentral.com)
- This domain occurred 402 times on human genes ( 935 proteins). (umbc.edu)
Serine1
- 2 , 3 CDK6 together with CDK4 are serine/threonine kinases that positively regulate the G1 phase progression in association with D-type cyclin. (ashpublications.org)
Glioblastoma1
- Long non-coding RNA CASP5 promotes the malignant phenotypes of human glioblastoma multiforme. (cancerindex.org)
Rabbit4
- Western blot analysis of extracts from various cell lines using CDK6 (E3E3Q) Rabbit mAb (upper) or GAPDH (D16H11) XP ® Rabbit mAb #5174 (lower). (cellsignal.com)
- using CDK6 (E3E3Q) Rabbit mAb (upper), Myc-Tag (71D10) Rabbit mAb #2278 (middle), or GAPDH (D16H11) XP ® Rabbit mAb #5174 (lower). (cellsignal.com)
- Western blot analysis was performed using CDK6 (E3E3Q) Rabbit mAb. (cellsignal.com)
- Immunohistochemical analysis of paraffin-embedded normal human colon (two fields of view) using CDK6 (E3E3Q) Rabbit mAb (left) or a CDK6 Rabbit mAb (right). (cellsignal.com)
Enzyme1
- Based on these findings, we identified the enzyme CDK6 as a potential drug target to prevent the immune overreaction in critical illness due to COVID-19. (medrxiv.org)
Primary microcephaly1
- Genes associated with the pathological reduction of brain size (primary microcephaly-MCPH) have the characteristics and functions to be considered ideal candidates to unravel the genetic basis of evolutionary enlargement of human brain size. (biomedcentral.com)
Lymphomas1
- It is a putative proto-oncogene overexpressed in a wide variety of human neoplasms including mantle cell lymphomas (MCL). (enquirebio.com)
Expression7
- Low expression of CDK6 protein in ZR-75-1, Neuro-2a, and INS-1 cells is consistent with the predicted expression pattern. (cellsignal.com)
- We hypothesized that a high fat diet in non-human primates would induce changes in hepatic chromatin structure resulting in altered expression of fetal genes critical to the development of childhood and adult obesity. (nih.gov)
- 4 However, no material was available for CDK6 expression analysis in this case. (ashpublications.org)
- This indicates that FISH and CDK6 expression analysis can be successfully used to identify patients with CDK6 involvement. (ashpublications.org)
- Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease. (nature.com)
- Expression of p16INK4a (p16 positive) is highly correlated with human papilloma virus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). (neobiotechnologies.com)
- High level SOX9 expression during development of the human embryonic pancreas is associated with abnormal islet formation in a case of Campomelic Dysplasia. (ncl.ac.uk)
Stem1
- CDK6 has also been found to be important in the development of other cell lines, for example, CDK6 has a role in the alteration of the morphology of astrocytes and in the development of other stem cells. (wikipedia.org)
PROTAC1
- CP-10 is a PROTAC with highly selective, specific, and remarkable CDK6 degradation (DC50=2.1 nM). (xcessbio.com)
Kinases1
- It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF-1, MOK, as well as eIF2 alpha kinases. (nih.gov)
Sequence3
- The human protein shares 94% and 95% aa sequence identity with the mouse and rat orthologs, respectively. (rndsystems.com)
- The t(7;14) involved the immunoglobulin heavy chain ( IgH ) locus in 14q32 and a transposon-like element located 29 kbp upstream of the CDK6 coding sequence. (ashpublications.org)
- The Human Genome Project has revealed that protein-coding genes represent less than 2% of the total genome sequence [ 7 ], and the remaining greater portion of human genomes are regarded as "junk DNAs", for they do not encode any protein. (oncotarget.com)
Targets1
- Additional algorithms predicted a higher miR-26b level was associated with significantly higher survival in CRC patients and GSK3β and CDK6 as targets of miR-26b-5p. (tmu.edu.tw)
Cancer6
- The mechanisms underlying the prosurvival function of cyclin D3-CDK6 have not been elucidated, prompting Wang and colleagues to search for substrates that may promote cancer cell survival. (aacrjournals.org)
- BEBT-209 is under clinical development by Guangzhou BeBetter Medicine Technology and currently in Phase I for Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer (HER2- Breast Cancer). (pharmaceutical-technology.com)
- According to GlobalData, Phase I drugs for Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer (HER2- Breast Cancer) have a 90% phase transition success rate (PTSR) indication benchmark for progressing into Phase II. (pharmaceutical-technology.com)
- 1) For example, the down-regulation of miR15s and miR - 16 - 1 in chronic lymphocytic leukaemia, prostate cancer and pituitary tumours, leading to the inhibition of tumour growth and induce cell cycle arrest at the G 1 - phase by target cell cycle regulators ( cyclin D1, cyclin E1, cyclin D3 and CDK6). (ukessays.com)
- Pancreatic cancer (PC) is a relatively common malignancy of the digestive system and one of the human malignancies with the worst prognosis [ 1 ]. (hindawi.com)
- Results: Bioinformatics analyses indicated that GSK3β/CDK6/β-catenin mRNA signature was significantly higher in colon cancer patients. (tmu.edu.tw)
Squamous cell carc2
- The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8 + T cells (Tex) in HNSCC. (elifesciences.org)
- Human cervical squamous cell carcinoma. (neobiotechnologies.com)
Ontology1
- RGD uses the Human Disease Ontology (DO, https://disease-ontology.org/) for disease curation across species. (mcw.edu)
Astrocytes1
- Importantly, normal human neurons and astrocytes remained impervious to the drug therapies under these conditions. (nih.gov)
Fibroblasts1
- B) INK4b and INK4a , but not ARF , are upregulated in ageing human diploid fibroblasts (HDFs). (biomedcentral.com)
Phosphorylation1
- Hsp90 interacts with Cdc37, is phosphorylated by PKA/PKC, and regulates Src phosphorylation in human sperm capacitation. (nih.gov)
Peripheral1
- Taken together, this study provides for the first time an in-depth analysis of the transcriptomic alterations that take place in human phagocytes upon infection, and in peripheral blood immune populations during active disease. (frontiersin.org)
Neutrophils1
- RNA sequencing was performed in primary human macrophages (Mφ) and polymorphonuclear neutrophils (PMNs) infected with a clinical strain of Brucella spp. (frontiersin.org)
MCPH1
- Contrary to our expectations, human-specific adoptive evolution was not detected for any of the MCPH genes analyzed in the present study. (biomedcentral.com)
Roles3
- This might hint additional roles of CDK6 in the development of blood components. (wikipedia.org)
- CDK6 differs from CDK4 in other important roles. (wikipedia.org)
- In addition, the potential for these genes to perform various cognitive roles during human brain evolutionary processes is discussed. (biomedcentral.com)
Regulators1
- Cyclin D1 or PRAD-1 or bcl-1 is one of the key cell cycle regulators, and functions in association with cdk4 and/or cdk6 by phosphorylating the Rb protein. (enquirebio.com)