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CIP2A inhibits PP2A in human malignancies

Melissa R Junttila1, Pietri Puustinen, Minna Niemelä

  • 1Centre for Biotechnology, University of Turku and Abo Akademi University, 20520 Turku, Finland.

Cell
|July 17, 2007
PubMed

Insights

Cancerous Inhibitor of PP2A (CIP2A) is a newly identified oncoprotein that inhibits protein phosphatase 2A (PP2A) activity. CIP2A stabilizes the oncogenic transcription factor c-Myc, promoting human cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein phosphatase 2A (PP2A) inhibition is crucial for human cell transformation.
  • The molecular mechanisms of PP2A inhibition in human cancers remain largely unknown.

Purpose of the Study:

  • To identify and characterize a cellular inhibitor of PP2A with oncogenic activity.
  • To elucidate the role of this inhibitor in human malignancies.

Main Methods:

  • Protein interaction studies to identify CIP2A.
  • Enzyme activity assays to measure PP2A inhibition.
  • Cellular assays for transformation and tumor formation.
  • Analysis of CIP2A expression in human cancers.

Main Results:

  • A novel protein, Cancerous Inhibitor of PP2A (CIP2A), was identified as a PP2A inhibitor.
  • CIP2A directly interacts with c-Myc, inhibiting PP2A activity at serine 62 (S62).
  • CIP2A prevents c-Myc degradation, promotes anchorage-independent growth, and induces tumor formation.
  • CIP2A is overexpressed in head and neck squamous cell carcinoma (HNSCC) and colon cancer.

Conclusions:

  • CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc.
  • CIP2A plays a significant role in the development of human malignancies.

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