Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 397, Issue 1, Pages 69-88Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2010.01.009
Keywords
centrosome; retrogene; Rab6A '; Rab6C; WTH3
Categories
Funding
- European Union [RTN-2002-00529]
- Agence Nationale pour la Recherche [Blan06-3-139786]
- Institut Curie
- Centre National de la Recherche Scientifique
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Rab-GTPases are key regulators of membrane transport, and growing evidence indicates that their expression levels are altered in certain human malignancies, including cancer. Rab6C, a newly identified Rab6 subfamily member, has attracted recent attention because its reduced expression might confer a selective advantage to drug-resistant breast cancer cells. Here, we report that RAB6C is a primate-specific retrogene derived from a RAB6A' transcript. RAB6C is transcribed in a limited number of human tissues including brain, testis, prostate, and breast. Endogenous Rab6C is considerably less abundant and has a much shorter half-life than Rab6A'. Comparison of the GTP-binding motifs of Rab6C and Rab6A', homology modeling, and GIP-blot overlay assays indicate that amino acid changes in Rab6C have greatly reduced its GTP-binding affinity. Instead, the noncanonical GIP-binding domain of Rab6C mediates localization of the protein to the centrosome. Overexpression of Rab6C results in Cl arrest, and its specific depletion generates tetraploid cells with supernumerary centrosomes, revealing a role of Rab6C in events related to the centrosome and cell cycle progression. Thus, RAB6C is a rare example of a recently emerged retrogene that has acquired the status of a new gene, encoding a functional protein with altered characteristics compared to Rab6A'. (C) 2010 Elsevier Ltd All rights reserved
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