The Parafibromin Tumor Suppressor Protein Is Part of a Human Paf1 Complex

Author:

Rozenblatt-Rosen Orit1,Hughes Christina M.1,Nannepaga Suraj J.1,Shanmugam Kalai Selvi1,Copeland Terry D.2,Guszczynski Tad2,Resau James H.3,Meyerson Matthew1

Affiliation:

1. Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts

2. Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute—Frederick, Frederick, Maryland

3. Analytical, Cellular, and Molecular Microscopy Laboratory, Van Andel Institute, Grand Rapids, Michigan

Abstract

ABSTRACT Parafibromin, the product of the HRPT2 (hyperparathyroidism-jaw tumor syndrome 2) tumor suppressor gene, is the human homologue of yeast Cdc73, part of the yeast RNA polymerase II/Paf1 complex known to be important for histone modification and connections to posttranscriptional events. By purifying cellular parafibromin and characterizing its associated proteins, we have identified a human counterpart to the yeast Paf1 complex including homologs of Leo1, Paf1, and Ctr9. Like the yeast complex, the parafibromin complex associates with the nonphosphorylated and Ser2 and Ser5 phosphorylated forms of the RNA polymerase II large subunit. Immunofluorescence experiments show that parafibromin is a nuclear protein. In addition, cotransfection data suggest that parafibromin can interact with a histone methyltransferase complex that methylates histone H3 on lysine 4. Some mutant forms of parafibromin lack association with hPaf1 complex members and with the histone methyltransferase complex, suggesting that disruption of these complexes may correlate with the oncogenic process.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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