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KIAA1524  -  KIAA1524

Homo sapiens

Synonyms: CIP2A, Cancerous inhibitor of PP2A, Protein CIP2A, p90, p90 autoantigen
 
 
Also known as Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) is an oncogene which interacts with MYC and stabilizes it by inhibiting its dephosphorylation by PP2A [1] Its clinical relevance was recently established as an oncoprotein overexpessed in human gastric cancer wherein it also serves as a prognostic marker in certain subgroups of gastric cancer patients. [2] Additionally, a positive feedback loop was shown to exist between MYC and CIP2A, wherein they promote each other's expression [2] CIP2A has also been shown to be assosciated with breast cancer aggressivity [3] Depletion of CIP2A lead to impaired clonogenicity, senescence, or differentiation of tumor cells [4] Recently , two other transcription factors, ETS-1 and E2F1 have been identified as positive regulators of this oncogene [5] [6]. Additionally, CIP2A has been demonstrated to play a crucial role in RAS-mediated cell transformation [7].

 

References

  1. CIP2A inhibits PP2A in human malignancies. Junttila, M.R., Puustinen, P., Niemelä, M., Ahola, R., Arnold, H., Böttzauw, T., Ala-aho, R., Nielsen, C., Ivaska, J., Taya, Y., Lu, S.L., Lin, S., Chan, E.K., Wang, X.J., Grènman, R., Kast, J., Kallunki, T., Sears, R., Kähäri, V.M., Westermarck, J. Cell. (2007) [Pubmed]
  2. MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. Khanna, A., Böckelman, C., Hemmes, A., Junttila, M.R., Wiksten, J.P., Lundin, M., Junnila, S., Murphy, D.J., Evan, G.I., Haglund, C., Westermarck, J., Ristimäki, A. J. Natl. Cancer. Inst. (2009) [Pubmed]
  3. CIP2A is associated with human breast cancer aggressivity. Côme, C., Laine, A., Chanrion, M., Edgren, H., Mattila, E., Liu, X., Jonkers, J., Ivaska, J., Isola, J., Darbon, J.M., Kallioniemi, O., Thézenas, S., Westermarck, J. Clin. Cancer. Res. (2009) [Pubmed]
  4. CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Li, W., Ge, Z., Liu, C., Liu, Z., Björkholm, M., Jia, J., Xu, D. Clin. Cancer. Res. (2008) [Pubmed]
  5. ETS1 mediates MEK1/2-dependent overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A) in human cancer cells. Khanna, A., Okkeri, J., Bilgen, T., Tiirikka, T., Vihinen, M., Visakorpi, T., Westermarck, J. PLoS. One. (2011) [Pubmed]
  6. Senescence sensitivity of breast cancer cells is defined by positive feedback loop between CIP2A and E2F1. Laine, A., Sihto, H., Come, C., Rosenfeldt, M.T., Zwolinska, A., Niemelä, M., Khanna, A., Chan, E.K., Kähäri, V.M., Kellokumpu-Lehtinen, P.L., Sansom, O.J., Evan, G.I., Junttila, M.R., Ryan, K.M., Marine, J.C., Joensuu, H., Westermarck, J. Cancer. Discov. (2013) [Pubmed]
  7. Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation. Mathiasen, D.P., Egebjerg, C., Andersen, S.H., Rafn, B., Puustinen, P., Khanna, A., Daugaard, M., Valo, E., Tuomela, S., Bøttzauw, T., Nielsen, C.F., Willumsen, B.M., Hautaniemi, S., Lahesmaa, R., Westermarck, J., Jäättelä, M., Kallunki, T. Oncogene. (2012) [Pubmed]
 
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