title: The parafibromin tumor suppressor protein is part of a human Paf1 complex.
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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
authors.forename: Orit
authors.initials: O
authors.lastname: Rozenblatt-Rosen
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hughes
authors.forename: Suraj J
authors.initials: SJ
authors.lastname: Nannepaga
authors.forename: Kalai Selvi
authors.initials: KS
authors.lastname: Shanmugam
authors.forename: Terry D
authors.initials: TD
authors.lastname: Copeland
authors.forename: Tad
authors.initials: T
authors.lastname: Guszczynski
authors.forename: James H
authors.initials: JH
authors.lastname: Resau
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011496:Protein Methyltransferases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D035602:Transcriptional Elongation Factors; D025521:Tumor Suppressor Proteins
chemical_list: C104439:CDC73 protein, S cerevisiae; C454900:CDC73 protein, human; C104718:CTR9 protein, S cerevisiae; D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors; D025521:Tumor Suppressor Proteins; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II; C410949:RNA polymerase II largest subunit