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

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.

SUBMITTER: Weterman MA

PROVIDER: S-EPMC61123 | biostudies-literature | 2001 Nov

REPOSITORIES: biostudies-literature

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

Weterman M A MA van Groningen J J JJ Tertoolen L L van Kessel A G AG

Proceedings of the National Academy of Sciences of the United States of America 20011101 24

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 rec ...[more]

PMID: 11717438

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