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

Journal Article · Fri Mar 20 04:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2009.01.171· OSTI ID:21255939

Wakoh, Takeshi; Uekawa, Natsuko ^[1]; Terauchi, Kunihiko ^[2]; Sugimoto, Masataka ^[1]; Ishigami, Akihito ^[3]; Shimada, Jun-ichi ^[2]; Maruyama, Mitsuo ^[1]

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1. 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)
2. Department of Cardiovascular and Thoracic Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566 (Japan)
3. Department of Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510 (Japan)

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{sup -/-} MEFs, we further suggest that this growth arrest by loss of TARSH is evoked by p53-dependent p21{sup 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.

• OSTI ID: 21255939
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 380; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BUDR
BUILDUP
CELL CYCLE
CELL PROLIFERATION
CHROMOSOMES
FIBROBLASTS
GALACTOSIDASE
GENES
INHIBITION
LUNGS
MICE
NEOPLASMS
RNA