KIAA1524
Protein CIP2A also known as cancerous inhibitor of PP2A (CIP2A) is a protein that in humans is encoded by the KIAA1524 gene.[1][2]
Function
Protein phosphatase 2A (PP2A) is a cellular tumor suppressor which inhibits cell proliferation and transformation of normal cells to malignant cancer cells. Inhibition of PP2A activity is a prerequisite for human cell transformation. However, the in vivo mechanisms by which PP2A activity is inhibited in spontaneously transformed human cancer cells have been unclear.
CIP2A inhibits PP2A tumor suppressor activity in human malignancies.[3] More specifically, CIP2A was demonstrated to inhibit PP2A activity towards oncogenic transcription factor c-Myc, and thereby prevent c-Myc proteolytic degradation. Moreover, CIP2A is required for the malignant cellular growth and for in vivo tumor formation. In accordance with the oncogenic role of CIP2A, overexpression of CIP2A promotes Ras-elicited cell growth and transforms immortalized human cells (HEK-TERVs).
Clinical significance
CIP2A is overexpressed in several common human malignancies including, human head and neck squamous cell carcinoma (HNSCC), colon cancer, gastric cancer, breast cancer, prostatecancer and lung cancer. Notably, in these cancer types CIP2A overexpression is observed with very high frequency; in breast cancer around 40% of cancer patients are overexpressing CIP2A whereas in all other studied cancer types the frequency is between 65-87 percent. In breast cancer CIP2A expression correlates with disease aggressivity whereas in gastric and lung cancer CIP2A expression predicts for poor patient survival.[4][5]
CIP2A is also over expressed in prostate cancer,[6] lung cancer,[7] oral squamous cell carcinoma,[8] and gastric cancer.[4] Furthermore, the expression of CIP2A correlates with breast cancer aggressivity.[9]
References
- ^ Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O (Sep 2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res 7 (2): 143–50. doi:10.1093/dnares/7.2.143. PMID 10819331.
- ^ "Entrez Gene: KIAA1524 KIAA1524". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57650.
- ^ Junttila MR, Puustinen P, Niemelä M, et al. (2007). "CIP2A inhibits PP2A in human malignancies". Cell 130 (1): 51–62. doi:10.1016/j.cell.2007.04.044. PMID 17632056.
- ^ a b Khanna A, Böckelman C, Hemmes A, Junttila MR, Wiksten JP, Lundin M, Junnila S, Murphy DJ, Evan GI, Haglund C, Westermarck J, Ristimäki A (June 2009). "MYC-dependent regulation and prognostic role of CIP2A in gastric cancer". J. Natl. Cancer Inst. 101 (11): 793–805. doi:10.1093/jnci/djp103. PMID 19470954.
- ^ Soo Hoo L, Zhang JY, Chan EK (2002). "Cloning and characterization of a novel 90 kDa 'companion' auto-antigen of p62 overexpressed in cancer". Oncogene 21 (32): 5006–15. doi:10.1038/sj.onc.1205625. PMID 12118381.
- ^ Vaarala MH, Väisänen MR, Ristimäki A (2010). "CIP2A expression is increased in prostate cancer". J. Exp. Clin. Cancer Res. 29 (1): 136. doi:10.1186/1756-9966-29-136. PMC 2984408. PMID 20964854. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2984408.
- ^ Dong QZ, Wang Y, Dong XJ, Li ZX, Tang ZP, Cui QZ, Wang EH (September 2010). "CIP2A is Overexpressed in Non-Small Cell Lung Cancer and Correlates with Poor Prognosis". Ann Surg Oncol 18 (3): 857–865. doi:10.1245/s10434-010-1313-8. PMID 20842459.
- ^ Basile JR, Czerninski R (November 2010). "The role of CIP2A in oral squamous cell carcinoma". Cancer Biol. Ther. 10 (7): 700–2. doi:10.4161/cbt.10.7.13151. PMID 20729627.
- ^ Côme C, Laine A, Chanrion M, Edgren H, Mattila E, Liu X, Jonkers J, Ivaska J, Isola J, Darbon JM, Kallioniemi O, Thézenas S, Westermarck J (August 2009). "CIP2A is associated with human breast cancer aggressivity". Clin. Cancer Res. 15 (16): 5092–100. doi:10.1158/1078-0432.CCR-08-3283. PMID 19671842.
Further reading
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311072.
- Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1083732.
- Soo Hoo L, Zhang JY, Chan EK (2002). "Cloning and characterization of a novel 90 kDa 'companion' auto-antigen of p62 overexpressed in cancer.". Oncogene 21 (32): 5006–15. doi:10.1038/sj.onc.1205625. PMID 12118381.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528930.
- Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1347501.
- Junttila MR, Puustinen P, Niemelä M, et al. (2007). "CIP2A inhibits PP2A in human malignancies.". Cell 130 (1): 51–62. doi:10.1016/j.cell.2007.04.044. PMID 17632056.