RABL6A, a Novel RAB-Like Protein, Controls Centrosome Amplification and Chromosome Instability in Primary FibroblastsReport as inadecuate




RABL6A, a Novel RAB-Like Protein, Controls Centrosome Amplification and Chromosome Instability in Primary Fibroblasts - Download this document for free, or read online. Document in PDF available to download.

RABL6A RAB-like 6 isoform A is a novel protein that was originally identified based on its association with the Alternative Reading Frame ARF tumor suppressor. ARF acts through multiple p53-dependent and p53-independent pathways to prevent cancer. How RABL6A functions, to what extent it depends on ARF and p53 activity, and its importance in normal cell biology are entirely unknown. We examined the biological consequences of RABL6A silencing in primary mouse embryo fibroblasts MEFs that express or lack ARF, p53 or both proteins. We found that RABL6A depletion caused centrosome amplification, aneuploidy and multinucleation in MEFs regardless of ARF and p53 status. The centrosome amplification in RABL6A depleted p53−-− MEFs resulted from centrosome reduplication via Cdk2-mediated hyperphosphorylation of nucleophosmin NPM at threonine-199. Thus, RABL6A prevents centrosome amplification through an ARF-p53-independent mechanism that restricts NPM-T199 phosphorylation. These findings demonstrate an essential role for RABL6A in centrosome regulation and maintenance of chromosome stability in non-transformed cells, key processes that ensure genomic integrity and prevent tumorigenesis.



Author: Xuefeng Zhang, Jussara Hagen, Viviane P. Muniz, Tarik Smith, Gary S. Coombs, Christine M. Eischen, Duncan I. Mackie, David L. Rom

Source: http://plos.srce.hr/



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