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Publication : Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression.

First Author  Wakoh T Year  2009
Journal  Biochem Biophys Res Commun Volume  380
Issue  4 Pages  807-12
PubMed ID  19338757 Mgi Jnum  J:147344
Mgi Id  MGI:3840370 Doi  10.1016/j.bbrc.2009.01.171
Citation  Wakoh T, et al. (2009) Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression. Biochem Biophys Res Commun 380(4):807-12
abstractText  A novel target of NESH-SH3 (TARSH) was identified as a cellular senescence related gene in mouse embryonic fibroblasts (MEFs) replicative senescence, the expression of which has been suppressed in primary clinical lung cancer specimens. However, the molecular mechanism underlying the regulation of TARSH involved in pulmonary tumorigenesis remains unclear. Here we demonstrate that the reduction of TARSH gene expression by short hairpin RNA (shRNA) system robustly inhibited the MEFs proliferation with increase in senescence-associated beta-galactosidase (SA-beta-gal) activity. Using p53-/- MEFs, we further suggest that this growth arrest by loss of TARSH is evoked by p53-dependent p21(Cip1) accumulation. Moreover, we also reveal that TARSH reduction induces multicentrosome in MEFs, which is linked in chromosome instability and tumor development. These results suggest that TARSH plays an important role in proliferation of replicative senescence and may serve as a trigger of tumor development.
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