Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas.
The papillary renal cell carcinoma (RCC)-associated (X;1)(p11;q21) translocation fuses the genes PRCC and TFE3 and leads to cancer by an unknown molecular mechanism. We here demonstrate that the mitotic checkpoint protein MAD2B interacts with PRCC. The PRCCTFE3 fusion protein retains the MAD2B interaction domain, but this interaction is impaired. In addition, we show that two t(X;1)-positive RCC tumor cell lines are defective in their mitotic checkpoint. Transfection of PRCCTFE3, but not the reciprocal product TFE3PRCC, disrupts the mitotic checkpoint in human embryonic kidney cells. Our results suggest a dominant-negative effect of the PRCCTFE3 fusion gene leading to a mitotic checkpoint defect as an early event in papillary RCCs.
Weterman
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MA
Department of Human Genetics, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands. A.Geurtsvankessel@antrg.azn.nl
van Groningen
J J
JJ
Tertoolen
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L
van Kessel
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AG
D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D019556:COS Cells; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D018797:Cell Cycle Proteins; D002522:Chlorocebus aethiops; D002878:Chromosomes, Human, Pair 1; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D064246:Mad2 Proteins; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011233:Precipitin Tests; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014178:Translocation, Genetic; D020798:Two-Hybrid System Techniques; D014960:X Chromosome
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D009363:Neoplasm Proteins; C415042:PRCC protein, human; D011506:Proteins; C069203:TFE3 protein, human; D014157:Transcription Factors