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The parafibromin tumor suppressor protein is part of a human Paf1 complex

Orit Rozenblatt-Rosen1, Christina M Hughes, Suraj J Nannepaga

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.

Molecular and Cellular Biology
|January 6, 2005
PubMed

Insights

Parafibromin, a tumor suppressor, forms a human complex similar to yeast

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Biology

Background:

  • Parafibromin, encoded by the HRPT2 tumor suppressor gene, is the human homolog of yeast Cdc73.
  • The yeast Cdc73 protein is a component of the RNA polymerase II/Paf1 complex, crucial for histone modification and RNA processing.

Purpose of the Study:

  • To identify and characterize the human parafibromin complex and its functions.
  • To investigate the association of parafibromin with RNA polymerase II and histone modification machinery.

Main Methods:

  • Purification of cellular parafibromin and associated proteins.
  • Characterization of the human parafibromin complex using biochemical and immunofluorescence techniques.
  • Cotransfection assays to study protein interactions.

Main Results:

  • A human counterpart to the yeast Paf1 complex, including homologs of Leo1, Paf1, and Ctr9, was identified.
  • The parafibromin complex associates with various forms of RNA polymerase II.
  • Parafibromin interacts with a histone methyltransferase complex involved in histone H3 lysine 4 methylation.
  • Mutant parafibromin proteins show disrupted complex formation, potentially linking to oncogenesis.

Conclusions:

  • Parafibromin is a nuclear protein that forms a complex with human Paf1 (hPaf1) components.
  • The parafibromin complex interacts with RNA polymerase II and histone modification enzymes.
  • Disruption of these interactions may contribute to the development of cancer.

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