PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors.
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.
Skalsky
Y M
YM
Institute of Cancer Research, Molecular Carcinogenesis Section, The Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Ajuh
P M
PM
Parker
C
C
Lamond
A I
AI
Goodwin
G
G
Cooper
C S
CS
D000328:Adult; D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D019677:Artificial Gene Fusion; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D000068103:Serine-Arginine Splicing Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000546:Amanitins; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C415042:PRCC protein, human; D011506:Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; C069203:TFE3 protein, human; D014157:Transcription Factors; C073288:SRSF2 protein, human; D049452:Green Fluorescent Proteins; D000068103:Serine-Arginine Splicing Factors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae