RABL6A, a novel RAB-like protein, controls centrosome amplification and chromosome instability in primary fibroblasts.

Zhang X, Hagen J, Muniz VP, Smith T, Coombs GS, Eischen CM, Mackie DI, Roman DL, Van Rheeden R, Darbro B, Tompkins VS, Quelle DE
PLoS One. 2013 8 (11): e80228

PMID: 24282525 · PMCID: PMC3839920 · DOI:10.1371/journal.pone.0080228

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.

MeSH Terms (13)

ADP-Ribosylation Factors Animals Centrosome Chromosomal Instability Fibroblasts Gene Knockout Techniques Gene Silencing Humans Mice Nuclear Proteins Oncogene Proteins rab GTP-Binding Proteins Tumor Suppressor Protein p53

Connections (1)

This publication is referenced by other Labnodes entities:

Links