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Related Experiment Videos

PP2A: the expected tumor suppressor.

Veerle Janssens1, Jozef Goris, Christine Van Hoof

  • 1Afdeling Biochemie, KU Leuven, Faculteit Geneeskunde, Campus Gasthuisberg, Herestraat 49 Bus 901, B-3000 Leuven, Belgium.

Current Opinion in Genetics & Development
|January 22, 2005
PubMed
Summary

Suppression of a protein phosphatase 2A (PP2A) regulatory subunit can cause cell transformation, mimicking viral oncogenes. This occurs with specific co-factors, highlighting PP2A

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Area of Science:

  • Cellular biology
  • Molecular oncology
  • Virology

Background:

  • Protein phosphatase 2A (PP2A) is a key serine/threonine phosphatase regulating diverse cellular functions.
  • Viruses often hijack host cell machinery, including PP2A, for replication and to induce malignant transformation.
  • The SV40 small t antigen is a known viral oncoprotein that targets PP2A.

Purpose of the Study:

  • To investigate the role of the PP2A regulatory subunit PR61/B'gamma in cellular transformation.
  • To determine if PR61/B'gamma can substitute for viral oncogenes in inducing tumorigenesis.
  • To identify common molecular denominators in PP2A-mediated transformation.

Main Methods:

  • Investigated the effects of suppressing PR61/B'gamma in human cell lines.

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  • Assessed tumorigenic transformation in the presence of other oncogenic factors (telomerase, SV40 large T antigen, oncogenic Ras).
  • Analyzed the accumulation of c-Myc as a potential common pathway.

    • Main Results:

    • Suppression of PR61/B'gamma, along with specific co-factors, induced tumorigenic transformation in human cell lines.
    • This effect mimicked the oncogenic activity of the SV40 small t antigen.
    • Accumulation of c-Myc was observed as a common molecular event.

    Conclusions:

    • The PP2A regulatory subunit PR61/B'gamma plays a critical role in cellular transformation.
    • Targeting PP2A subunits can be an alternative mechanism for viral oncogenesis.
    • c-Myc accumulation is a key downstream event in PP2A-mediated malignant transformation.