• Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. (koreamed.org)
  • CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. (wikipedia.org)
  • also known as CDK4I, Cyclin-dependent kinase 4 inhibitor A, Multiple tumor suppressor 1, MTS-1, p16-INK4, p16-INK4a, p16INK4A) is encoded by the CDKN2A (also known as CDKN2, MTS1) gene (Gene ID 1029) in human. (sigmaaldrich.com)
  • A different type of alteration involving the CDKN2A gene can result in reduced amounts or an absence of the p16(INK4A) or p14(ARF) protein. (medlineplus.gov)
  • The CDKN2A gene mutations found in melanoma result in a nonfunctional p16(INK4A) protein. (medlineplus.gov)
  • CDKN2A gene mutations involved in cancer impair production of functional p16(INK4A) or, less commonly, p14(ARF), which can result in uncontrolled cell growth and tumor formation. (medlineplus.gov)
  • Synthetic peptide corresponding to Mouse CDKN2A/p19ARF conjugated to keyhole limpet haemocyanin. (abcam.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)
  • The p16(Ink4a) and p19(Arf) knockout mice were generated via transcription activator-like effector nucleases (TALENs), and p27(Kip1) knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). (koreamed.org)
  • lt;div class="textblock">Oncogenic Ras induces two products of the INK4a/ARF tumor suppressor locus (p16(INK4a) and p19(ARF)) in primary human and rodent fibroblasts, ultimately leading to a permanent state of cell cycle arrest resembling replicative senescence. (ku.dk)
  • Whereas p16(INK4a) antagonizes the activities of cyclin D-dependent kinases, p19(ARF) activates the p53 transcription factor. (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)
  • No. MABE1451, is a highly specific mouse monoclonal antibody that targets INK4a (p16) and has been tested in Immunocytochemistry and Western Blotting. (sigmaaldrich.com)
  • The most well-studied are the p16(INK4A) and the p14(ARF) proteins. (medlineplus.gov)
  • The p16(INK4A) protein attaches (binds) to two other proteins called CDK4 and CDK6. (medlineplus.gov)
  • However, binding of p16(INK4A) blocks CDK4's or CDK6's ability to stimulate cell cycle progression. (medlineplus.gov)
  • In this way, p16(INK4A) controls cell division. (medlineplus.gov)
  • Cells begin to produce p16(INK4A) when they are no longer able to undergo cell division. (medlineplus.gov)
  • Most of these mutations lead to production of little or no functional p16(INK4A) protein. (medlineplus.gov)
  • Without p16(INK4A) to regulate cell growth and division (proliferation), cells can continue to grow and divide without control, which can lead to tumor formation. (medlineplus.gov)
  • This alteration, known as promoter hypermethylation, turns off the production of p16(INK4A) or p14(ARF). (medlineplus.gov)
  • We did simultaneous introduction of two tumor suppressor peptides (p14 ARF and p16 INK4a or p16 INK4a and p21 CIP1 functional peptides) compared with single-peptide introduction using Wr-T-mediated peptide delivery. (aacrjournals.org)
  • 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)
  • p16 Ink4a downregulation leads to an activation of PKA-CREB-PGC1α signaling through increased phosphorylation of PKA regulatory subunits. (diabetesjournals.org)
  • Taken together, these results provide evidence that p16 Ink4a controls fasting glucose homeostasis and could as such be involved in T2D development. (diabetesjournals.org)
  • Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. (koreamed.org)
  • The gene codes for two proteins, including the INK4 family member p16 (or p16INK4a) and p14arf. (wikipedia.org)
  • Expression of p16INK4a (p16 positive) is highly correlated with human papilloma virus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). (neobiotechnologies.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)
  • p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins, which block traversal from G1 to S-phase. (wikipedia.org)
  • It binds to CDK4/6 inhibiting its kinase activity and prevents Rb phosphorylation. (wikipedia.org)
  • It is a specific inhibitor of cdk4/cdk6, and a tumor suppressor involved in the pathogenesis of a variety of malignancies. (neobiotechnologies.com)
  • p16 interacts with cdk4. (uth.edu)
  • This interaction was modeled on a demonstrated interaction between human p16 and cdk4 from an unspecified species. (uth.edu)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. (rc-crispr.com)
  • In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. (rc-crispr.com)
  • Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. (ku.dk)
  • PTEN encodes a protein kinase of the same name and functions as a tumor suppressor through regulation of cell proliferation. (medscape.com)
  • P16/Rb pathway collaborates with the mitogenic signaling cascade for the induction of reactive oxygen species, which activates the protein kinase C delta, leading to an irreversible cell cycle arrest. (wikipedia.org)
  • Thus P16 participates not only in the initiation but also in the maintenance of cellular senescence, as well in tumor suppression. (wikipedia.org)
  • Two tumor suppressor proteins p53 and p16 are responsible for cellular senescence 4 . (ijpsr.com)
  • p14ARF (known as p19ARF in the mouse) activates the p53 tumor suppressor. (wikipedia.org)
  • This gene encodes two proteins, p16 and p14ARF, which are transcribed from the same second and third exons but alternative first exons: p16 from exon 1α and ARF from exon 1β. (wikipedia.org)
  • It is the physiological inhibitor of MDM2, an E3 ubiquitin ligase controlling the activity and stability of P53, and loss of P14ARF activity may have a similar effect as loss of P53. (wikipedia.org)
  • P14ARF induces cell cycle arrest in G2 phase and subsequent apoptosis in a P53-dependent and P53-independent manner, and thus is regarded as a tumor suppressor. (wikipedia.org)
  • In addition, P14ARF could down-regulate E2F-dependent transcription and plays a role in the control of the G1 to S phase transition as well. (wikipedia.org)
  • UniProt P42771-3), p14ARF/p19ARF or smARF (UniProt Q8N726-1 and Q8N726-2). (sigmaaldrich.com)
  • When external stressors such as telomere damage, oxidative stress (RAS activity) or epigenetic stress has been encountered by the cells, it activates ATM/ARF and p19ARF which in turn activates p53 pathway 6 . (ijpsr.com)
  • In the p53 pathway, the gene activates its transcriptional target p21 which is an inhibitor of cyclin / cdk2 as they work for the progression of replication and inactivates RB. (ijpsr.com)
  • On the other hand, some specific tumors harbor high levels of P16, and its function in limitation of tumorigenic progression has been inactivated via the loss of Rb. (wikipedia.org)
  • 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)
  • This locus, however, also encodes a protein from an alternative reading frame, designated p19ARF. (medscape.com)
  • Classical NF-κB is a cytoplasmic inactive heterodimer of p65 and p50 bound to Inhibitor of NF-κB (IκB) proteins [ 9 ]. (oncotarget.com)
  • TRADD recruits additional proteins that indirectly activate IκB kinase (IKK). (oncotarget.com)
  • 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)
  • In addition to p16 and ARF, this gene produces 4 other isoforms through alternative splicing. (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)
  • P16 interacts with Rb and controls the G1 to S transition. (wikipedia.org)
  • The INK and CIP/KIP families of cyclin dependent kinase inhibitors (CDKis) protect cells from oncogenic signals-initiated cellular transformation. (sigmaaldrich.com)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • During this process, a feedback loop exists between P16 and Rb, and P16 expression is controlled by Rb. (wikipedia.org)
  • Senescent cells show a distinctive feature called Senescent associated secretory phenotypes (SASP) which includes increased expression of p16 and Beta-galactosidase can be used as a marker for senescent cells. (ijpsr.com)
  • Increased expression of p16 and β -galactosidase can be used as markers to identify senescent cells. (ijpsr.com)
  • A and B) Representative views of the transcription activator-like effector nuclease (TALEN) targeting strategy for generation of p19Arf KO mice in both FVB (A) and B6 (B) strains. (koreamed.org)
  • Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. (koreamed.org)
  • Figure 2 TALEN-mediated generation of a p19Arf knockout mouse model. (koreamed.org)
  • p16 status is an important prognostic indicator in HNSCC and the p16 positive/HPV16 negative group is likely a distinct subgroup lacking any HPV genotype. (neobiotechnologies.com)
  • According to its solvent-accessible surface representation, p16 features clustered charged groups on its surface and a pocket located on the right side with a negatively charged left inner wall and a positively charged right inner wall. (wikipedia.org)