2. Academic Validation
  3. Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas

Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas

  • Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13808-13. doi: 10.1073/pnas.241304198.
M A Weterman 1,  J J van Groningen,  L Tertoolen,  A G van Kessel
Affiliations

Affiliation

  • 1 Department of Human Genetics, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands. A.Geurtsvankessel@antrg.azn.nl
PMID: 11717438 DOI: 10.1073/pnas.241304198
Abstract

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.

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