title: Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression.
abstract: 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.
authors.affiliation: Department of Mechanism of Aging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3, Gengo, Morioka-Cho, Obu-City, Aichi 474-8522, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wakoh
authors.forename: Natsuko
authors.initials: N
authors.lastname: Uekawa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Terauchi
authors.forename: Masataka
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Shimada
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Maruyama