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Critical roles of p53 and p16 in selenium‐induced senescence
Author(s) -
Wu Min,
Wang Thomas T.Y.,
Wu Ryan T.Y.,
Cheng WenHsing
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.786.12
Subject(s) - senescence , selenium , microbiology and biotechnology , biology , chemistry , organic chemistry
We have reported recently that selenium compounds can induce an ATM‐dependent senescence response that depends on reactive oxygen species in normal pulmonary and colorectal cells at doses ≤ LD 50 [Wu et al. 2010 J. Biol. Chem., 285, 12055–12062]. The ATM kinase plays a central role in DNA damage response and senescence, two early barriers of tumorigenesis. The tumor suppressor p53 is a substrate of the ATM kinase and plays an important role in oncogene‐induced senescence. Moreover, p16 expression is known to be up‐regulated and keep senescent cells in check. To elucidate the mechanism by which selenium compounds activate the ATM‐dependent senescence, here we studied the role of p53 and p16 in the senescence induction. We observed an increase in p16 protein levels 7 days after treatment of the MRC‐5 normal pulmonary cells with methylseleninic acid (MSeA, 1 μM) when senescence is induced. Results from senescence‐associated expression of β‐galactosidase assays showed that p53 shRNA MRC‐5 cells are deficient in senescence induction after treatment of MSeA (0–10 μM) for 48 h, followed by a recovery of 1–7 days. Taken together, these results implicate p53 and p16 in the MSeA‐induced senescence response, providing mechanistic insight into selenium chemoprevention that targets the ATM‐mediated early barriers of tumorigenesis. Grant Funding Source : UMCP