INK4

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]

  1. ^ a b Kim 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.
  2. ^ 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.
  3. ^ a b Cánepa 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.
  4. ^ 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.