CDK2AP1 explained

Cyclin-dependent kinase 2-associated protein 1 is an enzyme that in humans is encoded by the CDK2AP1 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a specific CDK2-associated protein, which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. This protein was found to also interact with DNA polymerase alpha/primase and mediate the phosphorylation of the large p180 subunit, which suggested the regulatory role in DNA replication during S phase of the cell cycle. A similar gene in hamster was isolated from, and functions as a growth suppressor of normal keratinocytes.

Interactions

CDK2AP1 has been shown to interact with Cyclin-dependent kinase 2.^[4]

It interacts with unnamed protein product (BC006130) which may mediate inhibitory effect of CDK2AP1 on cell proliferation.^[5]

Further reading

• Matsuo K, Shintani S, Tsuji T, Nagata E, Lerman M, McBride J, Nakahara Y, Ohyama H, Todd R, Wong DT . p12(DOC-1), a growth suppressor, associates with DNA polymerase alpha/primase . FASEB J. . 14 . 10 . 1318–24 . 2000 . 10877824 . 10.1096/fj.14.10.1318 . free .
• Shintani S, Ohyama H, Zhang X, McBride J, Matsuo K, Tsuji T, Hu MG, Hu G, Kohno Y, Lerman M, Todd R, Wong DT . p12DOC-1 Is a Novel Cyclin-Dependent Kinase 2-Associated Protein . Mol. Cell. Biol. . 20 . 17 . 6300–7 . 2000 . 10938106 . 86104 . 10.1128/MCB.20.17.6300-6307.2000 .
• Yuan Z, Sotsky Kent T, Weber TK . Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer . Oncogene . 22 . 40 . 6304–10 . 2003 . 13679870 . 10.1038/sj.onc.1206609 . 24498031 .
• Hu MG, Hu GF, Kim Y, Tsuji T, McBride J, Hinds P, Wong DT . Role of p12(CDK2-AP1) in transforming growth factor-beta1-mediated growth suppression . Cancer Res. . 64 . 2 . 490–9 . 2004 . 14744761 . 10.1158/0008-5472.CAN-03-2284 . 2905417 .
• Buajeeb W, Zhang X, Ohyama H, Han D, Surarit R, Kim Y, Wong DT . Interaction of the CDK2-associated protein-1, p12(DOC-1/CDK2AP1), with its homolog, p14(DOC-1R) . Biochem. Biophys. Res. Commun. . 315 . 4 . 998–1003 . 2004 . 14985111 . 10.1016/j.bbrc.2004.02.003 .
• Kim Y, Ohyama H, Patel V, Figueiredo M, Wong DT . Mutation of Cys105 inhibits dimerization of p12CDK2-AP1 and its growth suppressor effect . J. Biol. Chem. . 280 . 24 . 23273–9 . 2005 . 15840587 . 10.1074/jbc.M412929200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Peng H, Shintani S, Kim Y, Wong DT . Loss of p12CDK2-AP1 Expression in Human Oral Squamous Cell Carcinoma with Disrupted Transforming Growth Factor-β-Smad Signaling Pathway . Neoplasia . 8 . 12 . 1028–36 . 2007 . 17217620 . 1783720 . 10.1593/neo.06580 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein–protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
• Shin J, Yuan Z, Fordyce K, Sreeramoju P, Kent TS, Kim J, Wang V, Schneyer D, Weber TK . A del T poly T (8) mutation in the 3' untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC) . Surgery . 142 . 2 . 222–7 . 2007 . 17689689 . 10.1016/j.surg.2007.04.002 .

Notes and References

1. Daigo Y, Suzuki K, Maruyama O, Miyoshi Y, Yasuda T, Kabuto T, Imaoka S, Fujiwara T, Takahashi E, Fujino MA, Nakamura Y . Isolation, mapping and mutation analysis of a human cDNA homologous to the doc-1 gene of the Chinese hamster, a candidate tumor suppressor for oral cancer . Genes Chromosomes Cancer . 20 . 2 . 204–7 . November 1997 . 9331572 . 10.1002/(SICI)1098-2264(199710)20:2<204::AID-GCC12>3.0.CO;2-Q . 9615947 .
2. Tsuji T, Duh FM, Latif F, Popescu NC, Zimonjic DB, McBride J, Matsuo K, Ohyama H, Todd R, Nagata E, Terakado N, Sasaki A, Matsumura T, Lerman MI, Wong DT . Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene Doc-1 . J Biol Chem . 273 . 12 . 6704–9 . April 1998 . 9506968 . 10.1074/jbc.273.12.6704 . free .
3. Web site: Entrez Gene: CDK2AP1 CDK2-associated protein 1.
4. Shintani S, Ohyama H, Zhang X, McBride J, Matsuo K, Tsuji T, Hu MG, Hu G, Kohno Y, Lerman M, Todd R, Wong DT . p12DOC-1 Is a Novel Cyclin-Dependent Kinase 2-Associated Protein . Mol. Cell. Biol. . 20 . 17 . 6300–7 . September 2000 . 10938106 . 86104 . 10.1128/MCB.20.17.6300-6307.2000 .
5. Liu L, Yang X, Ni Q, Xiao Z, Zhao Y, Han J, Sun M, Chen B . Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle. . Mol Med Rep . 9 . 1 . 156–62 . Jan 2014 . 24248101 . 10.3892/mmr.2013.1801. free .