title: Growth factor dependent regulation of centrosome function and genomic instability by HuR.
abstract: The mRNA binding protein HuR is over expressed in cancer cells and contributes to disease progression through post-transcriptional regulation of mRNA. The regulation of HuR and how this relates to glioma is the focus of this report. SRC and c-Abl kinases regulate HuR sub-cellular trafficking and influence accumulation in the pericentriolar matrix (PCM) via a growth factor dependent signaling mechanism. Growth factor stimulation of glioma cell lines results in the associate of HuR with the PCM and amplification of centrosome number. This process is regulated by tyrosine phosphorylation of HuR and is abolished by mutating tyrosine residues. HuR is overexpressed in tumor samples from patients with glioblastoma and associated with a reduced survival. These findings suggest HuR plays a significant role in centrosome amplification and genomic instability, which contributes to a worse disease outcome.
authors: Department of Neurology, University of Alabama at Birmingham, 510 20th Street South, FOT 1020, Birmingham, AL 35209, USA. as1999@uab.edu.
authors: Natalia
authors: N
authors: Filippova
authors: Department of Neurology, University of Alabama at Birmingham, 510 20th Street South, FOT 1020, Birmingham, AL 35209, USA. xiuhua@uab.edu.
authors: Xiuhua
authors: X
authors: Yang
authors: Department of Neurology, University of Alabama at Birmingham, 510 20th Street South, FOT 1020, Birmingham, AL 35209, USA. bnabors@uab.edu.
authors: Louis Burt
authors: LB
authors: Nabors
mesh_terms: D045744:Cell Line, Tumor; D018385:Centrosome / Q000187:drug effects* / Q000378:metabolism*; D051959:ELAV Proteins / Q000737:chemistry / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D042822:Genomic Instability / Q000187:drug effects*; D005910:Glioma / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051959:ELAV Proteins; D036341:Intercellular Signaling Peptides and Proteins; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases