A1 Refereed original research article in a scientific journal
CIP2A inhibits PP2A in human malignancies
Authors: Junttila MR, Puustinen P, Niemela M, Ahola R, Arnold H, Bottzauw T, Ala-Aho R, Nielsen C, Ivaska J, Taya Y, Lu SL, Lin SJ, Chan EKL, Wang XJ, Grenman R, Kast J, Kallunki T, Sears R, Kahari VM, Westermarck J
Publisher: CELL PRESS
Publication year: 2007
Journal: Cell
Journal name in source: CELL
Journal acronym: CELL
Volume: 130
Issue: 1
First page : 51
Last page: 62
Number of pages: 12
ISSN: 0092-8674
DOI: https://doi.org/10.1016/j.cell.2007.04.044
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 cMyc 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.
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 cMyc 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.
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