HUR DEPENDENT REGULATION OF CENTROSOMES

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Abstract

BACKGROUND: The RNA-binding protein, HuR is over-expressed in glioma and controls mRNA stabilization and translation in centrosomes. Alterations in HuR phosphorylation promote centrosomal abnormalities. METHODS: Primary and established glioma cell lines were utilized. Subcellular fractionation and immunofluorescence techniques were used to confirm localization of HuR in the PCM. Immunoprecipitation and kinase assays were used to document HuR interaction with and phosphorylation by SRC and ABL1. RESULTS: HuR association with the pericentriolar matrix (PCM) is growth factor dependent and facilitates centrosome amplification and genomic instability in glioma. The SRC and ABL1 kinases are possible regulators of the HuR association with pericentriolar matrix and phosphorylate HuR. CONCLUSIONS: HuR is involved in the regulation of genomic instability through growth factor and centrosome dependent pathways in glioma. We provide the evidence of HuR regulation by SRC and ABL1 kinases in U251 cells and discuss molecular and cellular consequences of this interaction. SECONDARY CATEGORY: n/a.

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