PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors

Oncogene. 2001 Jan 11;20(2):178-87. doi: 10.1038/sj.onc.1204056.

Abstract

In papillary renal cell carcinomas the TFE3 transcription factor becomes fused to the PSF and NonO pre-mRNA splicing factors and most commonly to a protein of unknown function designated PRCC. In this study we have examined the ability of the resulting PRCC-TFE3 and NonO-TFE3 fusions to activate transcription from the plasminogen activator inhibitor-1 (PAI-1) promoter. The results show that only fusion to PRCC enhanced transcriptional activation, indicating that the ability to enhance the level of transcription from endogenous TFE3 promoters is not a consistent feature of TFE3 fusions. In investigations of the normal function of PRCC we observed that PRCC expressed as a green fluorescent fusion protein colocalizes within the nucleus with Sm pre-mRNA splicing factors. It was also found that endogenous PRCC is coimmunoprecipitated by antibodies that recognize a variety of pre-mRNA splicing factors including SC35, PRL1 and CDC5. Association with the cellular splicing machinery is therefore, a common feature of the proteins that become fused to TFE3 in papillary renal cell carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amanitins / pharmacology
  • Animals
  • Artificial Gene Fusion
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Carcinoma, Papillary / drug therapy
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Cell Cycle Proteins*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Green Fluorescent Proteins
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Luminescent Proteins* / genetics
  • Luminescent Proteins* / metabolism
  • Male
  • Neoplasm Proteins*
  • Nuclear Proteins / metabolism*
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA Precursors / genetics
  • RNA Splicing
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins*
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Serine-Arginine Splicing Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • Amanitins
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Luminescent Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • PRCC protein, human
  • Proteins
  • RNA Precursors
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • Ribonucleoproteins, Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • TFE3 protein, human
  • Transcription Factors
  • SRSF2 protein, human
  • Green Fluorescent Proteins
  • Serine-Arginine Splicing Factors
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • CDC5 protein, S cerevisiae