INK4 is a family of cyclin-dependent kinase inhibitors (CKIs). The members of this family (p16INK4a, p15INK4b, p18INK4c, p19INK4d) are inhibitors of CDK4 (hence their name INhibitors of CDK4), and of CDK6. The other family of CKIs, CIP/KIP proteins are capable of inhibiting all CDKs. Enforced expression of INK4 proteins can lead to G1 arrest by promoting redistribution of Cip/Kip proteins and blocking cyclin E-CDK2 activity. In cycling cells, there is a resassortment of Cip/Kip proteins between CDK4/5 and CDK2 as cells progress through G1.[1] Their function, inhibiting CDK4/6, is to block progression of the cell cycle beyond the G1 restriction point.[2] In addition, INK4 proteins play roles in cellular senescence, apoptosis and DNA repair.[3]
INK4 proteins are tumor suppressors and loss-of-function mutations lead to carcinogenesis.[4]
INK4 proteins are highly similar in terms of structure and function, with up to 85% amino acid similarity.[1] They contain multiple ankyrin repeats.[3]
^ abKim WY, Sharpless NE (October 2006). "The regulation of INK4/ARF in cancer and aging". Cell. 127 (2): 265–75. doi:10.1016/j.cell.2006.10.003. PMID 17055429. S2CID 18280031.
^Ortega S, Malumbres M, Barbacid M (March 2002). "Cyclin D-dependent kinases, INK4 inhibitors and cancer". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1602 (1): 73–87. doi:10.1016/S0304-419X(02)00037-9. PMID 11960696.
^ abCánepa ET, Scassa ME, Ceruti JM, Marazita MC, Carcagno AL, Sirkin PF, Ogara MF (July 2007). "INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions". IUBMB Life. 59 (7): 419–26. doi:10.1080/15216540701488358. hdl:11336/30965. PMID 17654117. S2CID 9339088.
^Roussel MF (September 1999). "The INK4 family of cell cycle inhibitors in cancer". Oncogene. 18 (38): 5311–7. doi:10.1038/sj.onc.1202998. PMID 10498883.
INK4 is a family of cyclin-dependent kinase inhibitors (CKIs). The members of this family (p16INK4a, p15INK4b, p18INK4c, p19INK4d) are inhibitors of CDK4...
many tissues and cell types. The gene codes for two proteins, including the INK4 family member p16 (or p16INK4a) and p14arf. Both act as tumor suppressors...
isoform '4' encodes p14(ARF), a protein that is structurally unrelated to p16(INK4) but acts in cell cycle G1 control by stabilizing the tumor suppressor protein...
2005, ISBN 978-0-19-926472-8, Section 5.3 Roussel MF (September 1999). "The INK4 family of cell cycle inhibitors in cancer". Oncogene. 18 (38): 5311–5317...
Additionally, CDK4/6 and CDK2 are also inactive because CDK4/6 are bound by INK4 family members (e.g., p16), limiting kinase activity. Meanwhile, CDK2 complexes...
In 2009, Sharpless and his team were the first to discover altered human INK4/ARF expression as the mechanism for the 9p21.3 genetic risk allele of atherosclerosis...
which the arteries become hard. It has been proposed that cANRIL can modify INK4/ARF expression, which, in turn, increases risk for atherosclerosis. Further...
centlein CDKN2BAS: CDKN2B antisense RNA 1 or antisense non-coding RNA in the INK4 locus (ANRIL) COL5A1: collagen, type V, alpha 1 DDX31: DEAD box polypeptide...
CDKN2B-AS, also known as ANRIL (antisense non-coding RNA in the INK4 locus) is a long non-coding RNA consisting of 19 exons, spanning 126.3kb in the genome...
regulates G1-S progression of gastric cancer cells by modulation of multiple INK4 family tumor suppressors". Molecular Cancer Research. 7 (4): 570–80. doi:10...
by the CDKN2C gene. The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown...
and the G1-S transition are suppressed by cell cycle inhibitors including Ink4 and Cip/Kip family proteins. As a result, Rb is hypophosphorylated and inhibits...
cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. p14, p15, p16, p18). INK4 proteins are activated in response to hyperproliferative...
by the CDKN2D gene. The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown...
the expression of INK4/ARF tumor suppressor genes through a mechanism involving the epigenetic modification of chromatin at the INK4/ARF locus. In addition...
, Marazita, M.C., Carcagno, A.L., Sirkin, P.F., and Ogara, M.F. (2007). INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions...
Z (Jun 2000). "A minimum folding unit in the ankyrin repeat protein p16(INK4)". J Mol Biol. 299 (4): 1121–32. doi:10.1006/jmbi.2000.3803. PMID 10843863...
cyclin D acts as a mitogenic signal sensor. Cdk inhibitors (CKI), such as the Ink4 proteins and p21, help to prevent improper cyclin-cdk activity. Active cyclin...
Sharpless, NE (2010). "Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk". PLOS...
Vassilakis DA, Siafakas NM, Spandidos DA (2003). "MYCL1, FHIT, SPARC, p16(INK4) and TP53 genes associated to lung cancer in idiopathic pulmonary fibrosis"...
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