CIP2A Inhibits PP2A in Human Malignancies
Copyright policy )CIP2A Inhibits PP2A 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 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.
- Turku University Hospital Finland
- University of British Columbia Canada
- Tampere University Finland
- University of Turku Finland
- OREGON HEALTH AND SCIENCE UNIVERSITY
HUMDISEASE, Autoantigens/genetics, Cell Transformation, Autoantigens, Cell Line, Proto-Oncogene Proteins c-myc, SDG 3 - Good Health and Well-being, Animals, Humans, Protein Phosphatase 2/antagonists & inhibitors, Protein Phosphatase 2, Membrane Proteins/genetics, Enzyme Inhibitors, RNA, Small Interfering, Squamous Cell/genetics, Neoplastic, Biochemistry, Genetics and Molecular Biology(all), Carcinoma, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Colonic Neoplasms/genetics, Enzyme Inhibitors/metabolism, Head and Neck Neoplasms/genetics, Cell Transformation, Neoplastic, Small Interfering/genetics, SIGNALING, Head and Neck Neoplasms, Colonic Neoplasms, Carcinoma, Squamous Cell, RNA, Proto-Oncogene Proteins c-myc/genetics
HUMDISEASE, Autoantigens/genetics, Cell Transformation, Autoantigens, Cell Line, Proto-Oncogene Proteins c-myc, SDG 3 - Good Health and Well-being, Animals, Humans, Protein Phosphatase 2/antagonists & inhibitors, Protein Phosphatase 2, Membrane Proteins/genetics, Enzyme Inhibitors, RNA, Small Interfering, Squamous Cell/genetics, Neoplastic, Biochemistry, Genetics and Molecular Biology(all), Carcinoma, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Colonic Neoplasms/genetics, Enzyme Inhibitors/metabolism, Head and Neck Neoplasms/genetics, Cell Transformation, Neoplastic, Small Interfering/genetics, SIGNALING, Head and Neck Neoplasms, Colonic Neoplasms, Carcinoma, Squamous Cell, RNA, Proto-Oncogene Proteins c-myc/genetics
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