کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2185968 1096027 2010 20 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
RAB6C Is a Retrogene that Encodes a Centrosomal Protein Involved in Cell Cycle Progression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
RAB6C Is a Retrogene that Encodes a Centrosomal Protein Involved in Cell Cycle Progression
چکیده انگلیسی

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 GTP-blot overlay assays indicate that amino acid changes in Rab6C have greatly reduced its GTP-binding affinity. Instead, the noncanonical GTP-binding domain of Rab6C mediates localization of the protein to the centrosome. Overexpression of Rab6C results in G1 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′.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 397, Issue 1, 19 March 2010, Pages 69–88
نویسندگان
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