amanitins and Kidney-Neoplasms

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.

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