CIP/KIP

The CIP/KIP (CDK interacting protein/Kinase inhibitory protein) family is one of two families (CIP/KIP and INK4) of mammalian cyclin dependent kinase (CDK) inhibitors (CKIs) involved in regulating the cell cycle.[1][2] The CIP/KIP family is made up of three proteins: p21cip1/waf1,[3][4] P27kip1,[5] p57kip2[6][7] These proteins share sequence homology at the N-terminal domain which allows them to bind to both the cyclin and CDK. Their activity primarily involves the binding and inhibition of G1/S- and S-Cdks; however, they have also been shown to play an important role in activating the G1-CDKs CDK4 and CDK6.[8][9] In addition, more recent work has shown that CIP/KIP family members have a number of CDK-independent roles involving regulation of transcription, apoptosis, and the cytoskeleton.[10][11][12][13]

  1. ^ Morgan DO (2007). The Cell Cycle: Principles of Control. Primers in Biology.
  2. ^ Sherr CJ, Roberts JM (1999). "CDK inhibitors: positive and negative regulators of G1-phase progression". Genes & Development. 13 (12): 1501–1512. doi:10.1101/gad.13.12.1501. PMID 10385618.
  3. ^ Gu Y, Turek CW, Morgan DO (1993). "Inhibition of CDK 2 activity in vivo by an associated 20K regulatory subunit". Nature. 366 (6456): 707–710. Bibcode:1993Natur.366..707G. doi:10.1038/366707a0. PMID 8259216. S2CID 4368793.
  4. ^ Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D (1993). "p21 is a universal inhibitor of cyclin kinases". Nature. 366 (6456): 701–704. Bibcode:1993Natur.366..701X. doi:10.1038/366701a0. PMID 8259214. S2CID 4362507.
  5. ^ Toyoshima H, Hunter T (1994). "p27, a novel inhibitor of G1 cyclin/cdk protein kinase activity, is related to p21". Cell. 78 (1): 67–74. doi:10.1016/0092-8674(94)90573-8. PMID 8033213. S2CID 39776582.
  6. ^ Matsuoka S, Edwards M, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ (1995). "p57kip2, a structureally distinct member of the p21 cip1 cdk inhibitor family, is a candidate tumor suppressor gene". Genes & Development. 9 (6): 650–662. doi:10.1101/gad.9.6.650. PMID 7729684.
  7. ^ Lee MH, Reynisdottir I, Massague J (1995). "Cloning of p57kip2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution". Genes & Development. 9 (6): 639–649. doi:10.1101/gad.9.6.639. PMID 7729683.
  8. ^ Soos TJ, Kiyokawa H, Yan JS, Rubin MS, Giordano A, DeBlasio A, Bottega S, Wong B, Mendelsohn J, Koff A (1996). "Formation of p27-CDK complexes during the human mitotic cell cycle". Cell Growth & Differentiation. 7: 135–146.
  9. ^ LeBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E (1997). "New functional activities for the p21 family of CDK inhibitors". Genes & Development. 11 (7): 847–862. doi:10.1101/gad.11.7.847. PMID 9106657.
  10. ^ Coqueret O (2003). "New roles for p21 and p27 cell-cycle inhibitors: A function for each cell compartment?". Trends in Cell Biology. 13 (2): 65–70. doi:10.1016/S0962-8924(02)00043-0. PMID 12559756.
  11. ^ Nagahara H, Vocero-Akbani AM, Snyder EL, Ho A, Latham DG, Lissy NA, Becker-Hapak M, Ezhevsky SA, Dowdy SF (1998). "Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration". Nature Methods. 4 (12): 1449–1452. doi:10.1038/4042. PMID 9846587. S2CID 10962704.
  12. ^ Besson A, Gurian-West M, Schmidt A, Hall A, Roberts JM (2004). "p27Kip1 modulates cell migration through the regulation of RhoA activation". Genes & Development. 18 (8): 851–855. doi:10.1101/gad.1185504. PMC 395846. PMID 15078817.
  13. ^ Wang YA, Elson A, Leder P (1997). "Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice". PNAS. 94 (26): 14590–14595. Bibcode:1997PNAS...9414590W. doi:10.1073/pnas.94.26.14590. PMC 25064. PMID 9405657.