@article{50a9188cb00245edb2e77d41eecfb140,
title = "CIP2A Inhibits PP2A in Human Malignancies",
abstract = "Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.",
keywords = "HUMDISEASE, SIGNALING",
author = "Junttila, {Melissa R.} and Pietri Puustinen and Minna Niemel{\"a} and Raija Ahola and Hugh Arnold and Trine B{\"o}ttzauw and Risto Ala-aho and Christina Nielsen and Johanna Ivaska and Yoichi Taya and Lu, {Shi Long} and Shujun Lin and Chan, {Edward K.L.} and Wang, {Xiao Jing} and Reidar Gr{\`e}nman and Juergen Kast and Tuula Kallunki and Rosalie Sears and K{\"a}h{\"a}ri, {Veli Matti} and Jukka Westermarck",
note = "Funding Information: The expert technical assistance of Raisa Vuorinen and Sari Pitk{\"a}nen is gratefully acknowledged. We thank T. Vahlberg for help in statistical analysis, A. Laiho and Tia Heinonen for the microarray analysis, and E. Mattila for the help with mouse experiments. Special thanks to T. Junttila and K. Elenius for the analysis of CIP2A mRNA in normal tissues and to H. Nordlund and M. Kulomaa for CIP2A protein production. We thank C.M Counter, W.C. Hahn, B. Hemmings, and J. Peltonen for materials. This study was supported by the Academy of Finland (projects 878179, 8212695, 8105778, and 45996), Sigrid Jus{\'e}lius Foundation, the Cancer Research Foundation of Finland, Turku University Central Hospital (project 13336), and the European Union Framework Programme 6 (LSHC-CT-2003-503297; CANCERDEGRADOME). Grant support for Hugh Arnold was NIH T32-GM08617, for Rosalie Sears NIH R01-CA100855, and for Xiao-Jing Wang NIH DE15953. ",
year = "2007",
month = jul,
day = "13",
doi = "10.1016/j.cell.2007.04.044",
language = "English (US)",
volume = "130",
pages = "51--62",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",
}