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Identification of pVHL as a Novel Substrate for Aurora-A in Clear Cell Renal Cell Carcinoma (ccRCC)

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer and is often characterized by mutations or deletions of the Von Hippel Lindau (VHL) tumour suppressor gene. Aurora gene family members are implicated in proper mitotic progression and spindle checkpoint...

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Detalles Bibliográficos
Autores principales: Martin, Benedicte, Chesnel, Franck, Delcros, Jean-Guy, Jouan, Florence, Couturier, Anne, Dugay, Frederic, Le Goff, Xavier, Patard, Jean-Jacques, Fergelot, Patricia, Vigneau, Cecile, Rioux-Leclerq, Nathalie, Arlot-Bonnemains, Yannick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681765/
https://www.ncbi.nlm.nih.gov/pubmed/23785518
http://dx.doi.org/10.1371/journal.pone.0067071
Descripción
Sumario:Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer and is often characterized by mutations or deletions of the Von Hippel Lindau (VHL) tumour suppressor gene. Aurora gene family members are implicated in proper mitotic progression and spindle checkpoint function and play a crucial role in cancer progression. In the present study, we assessed the expression of Aurora-A in a cohort of 30 ccRCC with fully characterized VHL status (wt/wt or mut/del) and Fuhrman grade. Aurora-A transcript and protein levels were significantly increased in high Fuhrman grade tumours and in VHLwt/wt tumours. These results suggest that Aurora-A and VHL interact in the ccRCC. We demonstrated that the two proteins interact in vivo and identified the Ser72 on the sequence of VHL as the unique site phosphorylated by Aurora-A.