Phosphatase Subfamily CDKN3

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily CDKN3

CDKN3 is a cell cycle phosphatase that acts on Cyclin-dependent kinases (CDKs) CDK1/CDC2 and CDK2.

Evolution

CDKN3 is found in deuterostomes and scattered other bilaterians. These include basal arthropods (Ixodes, Zootermopsis), Lophotrochozoa (Aplysia, Lottia, Crassostrea) and some cnidarians (Acropora, Exaiptasia). It is not found in most insects or any nematodes. CDKN3 is most close in sequence to the PRL and PTPDC1 subfamilies.

Domain

CDKN3 has a single domain: phosphatase domain.

Function

CDKN3 is a cell cycle regulator. It dephosphorylates threonine-161 of CDC2/CDK1 during mitotic exit [1, 2]. CDKN3 also dephosphorylates threonine-160 CDK2 at the G1 to S transition but showed a preference for CDC2 [1, 3, 4].

CDKN3 is involved in cancer, but its role is controversial. CDKN3 acts as an oncogene in human hepatocellular carcinoma [5]. CDKN3 is over-expressed in renal cancer cells [6], breast and prostate cancer [7]. However, CDKN3 protein is down-regulated in brain tumors [2].

References

1. Hannon GJ, Casso D, and Beach D. KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1731-5. DOI:10.1073/pnas.91.5.1731 |
2. Nalepa G, Barnholtz-Sloan J, Enzor R, Dey D, He Y, Gehlhausen JR, Lehmann AS, Park SJ, Yang Y, Yang X, Chen S, Guan X, Chen Y, Renbarger J, Yang FC, Parada LF, and Clapp W. The tumor suppressor CDKN3 controls mitosis. J Cell Biol. 2013 Jun 24;201(7):997-1012. DOI:10.1083/jcb.201205125 |
3. Gyuris J, Golemis E, Chertkov H, and Brent R. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell. 1993 Nov 19;75(4):791-803. DOI:10.1016/0092-8674(93)90498-f |
4. Poon RY and Hunter T. Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin. Science. 1995 Oct 6;270(5233):90-3. DOI:10.1126/science.270.5233.90 |
5. Xing C, Xie H, Zhou L, Zhou W, Zhang W, Ding S, Wei B, Yu X, Su R, and Zheng S. Cyclin-dependent kinase inhibitor 3 is overexpressed in hepatocellular carcinoma and promotes tumor cell proliferation. Biochem Biophys Res Commun. 2012 Mar 30;420(1):29-35. DOI:10.1016/j.bbrc.2012.02.107 |
6. Lai MW, Chen TC, Pang ST, and Yeh CT. Overexpression of cyclin-dependent kinase-associated protein phosphatase enhances cell proliferation in renal cancer cells. Urol Oncol. 2012 Nov-Dec;30(6):871-8. DOI:10.1016/j.urolonc.2010.09.010 |
7. Lee SW, Reimer CL, Fang L, Iruela-Arispe ML, and Aaronson SA. Overexpression of kinase-associated phosphatase (KAP) in breast and prostate cancer and inhibition of the transformed phenotype by antisense KAP expression. Mol Cell Biol. 2000 Mar;20(5):1723-32. DOI:10.1128/MCB.20.5.1723-1732.2000 |