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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we have identified a novel centrosomal protein centrobin that asymmetrically localizes to the daughter centriole. We found that depletion of centrobin expression inhibited the centriole duplication and impaired cytokinesis. However, the biological significance of centrobin in the cell cycle remains unknown. In the current study, we observed that silencing centrobin significantly inhibited the proliferation of lung cancer cell A549 and prevented the cells from G1 to S transition, whereas the growth rate of lung cancer cell line H1299, a p53-null cell line, was not affected. Furthermore, we demonstrated that the G1-S-phase arrest induced by centrobin knockdown in A549 cells is mediated by the upregulation of cell-cycle regulator p53, which is associated with the activation of cellular stress induced p38 pathway instead of DNA damage induced ATM pathway. Inhibition of p38 activity or downregulation of p38 expression could overcome the cell-cycle arrest caused by centrobin depletion. Taken together, our current findings demonstrated that centrobin plays an important role in the progression of cell cycle, and a tight association between the cell-cycle progression and defective centrosomes caused by depletion of centrobin.
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PMID:Inhibition of centriole duplication by centrobin depletion leads to p38-p53 mediated cell-cycle arrest. 2008 6

DNA repair proteins have been found to localize to the centrosomes and defects in these proteins cause centrosome abnormality. Centrobin is a centriole-associated protein that is required for centriole duplication and microtubule stability. A recent study revealed that centrobin is a candidate substrate for ATM/ATR kinases. However, whether centrobin is involved in DNA damage response (DDR) remains unexplored. Here we show that centrobin is phosphorylated after UV exposure and that the phosphorylation is detected exclusively in the detergent/DNase I-resistant nuclear matrix. UV-induced phosphorylation of centrobin is largely dependent on ATR activity. Centrobin-depleted cells show impaired DNA damage-induced microtubule stabilization and increased sensitivity to UV radiation. Interestingly, depletion of centrobin leads to defective homologous recombination (HR) repair, which is reversed by expression of wild-type centrobin. Taken together, these results strongly suggest that centrobin plays an important role in DDR.
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PMID:Centrobin plays a role in the cellular response to DNA damage. 3141 97