Proteomic identification of a role for the von Hippel Lindau tumour suppressor in changes in the expression of mitochondrial proteins and septin 2 in renal cell carcinoma

RA Craven, S Hanrahan, N Totty, P Harnden, AJ Stanley, Eamonn Maher, AL Harris, WS Trimble

    Research output: Contribution to journalArticle

    55 Citations (Scopus)

    Abstract

    The von Hippel Lindau (VHL) tumour suppressor gene, VHL, plays a central role in development of sporadic conventional renal cell carcinomas (RCCs). Studying VHL function may, therefore, increase understanding of the pathogenesis of RCC and identify markers/therapeutic targets. Comparison of 2-DE protein profiles of VHL-defective RCC cells (UMRC2) transfected with control vector or wild-type VHL showed differences in 30 proteins, including several novel changes. One of the findings confirmed by Western blotting was up-regulation of the mitochondrial protein ubiquinol cytochrome c reductase complex core protein 2 following VHL transfection, a change that was also observed in two other cell line backgrounds. A marked decrease in expression of this and several other mitochondrial proteins was demonstrated in RCC tissues and using VHL-transfectants, several were shown to exhibit VHL-dependent regulation. Thus, VHL may contribute to the decreased mitochondrial function seen in RCC. A form of septin 2 down-regulated following VHL transfection was also identified. Septin 2 was up-regulated in 12/16 RCCs, while alteration of the form present was also observed in 1/3 tumours analysed. Thus, increased expression of septin 2 is a common event in RCC and protein modification may also alter septin 2 function in a subset of tumours.
    Original languageEnglish
    Pages (from-to)3880-3893
    Number of pages14
    JournalProteomics
    Volume6
    Issue number13
    DOIs
    Publication statusPublished - 1 Jul 2006

    Keywords

    • mitochondrial enzymes
    • septin
    • renal cancer
    • von Hippel Lindau
    • transfectants

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