ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation |
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| Authors: | Pedeux Remy Sengupta Sagar Shen Jiang Cheng Demidov Oleg N Saito Shin'ichi Onogi Hitoshi Kumamoto Kensuke Wincovitch Stephen Garfield Susan H McMenamin Mary Nagashima Makoto Grossman Steven R Appella Ettore Harris Curtis C |
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| Affiliation: | Laboratory of Human Carcinogenesis, CCR, NCI, NIH, 37 Convent Dr., Bldg 37, Room 3068, Bethesda, MD 20892-4255, USA. |
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| Abstract: | ING2 is a candidate tumor suppressor gene that can activate p53 by enhancing its acetylation. Here, we demonstrate that ING2 is also involved in p53-mediated replicative senescence. ING2 protein expression increased in late-passage human primary cells, and it colocalizes with serine 15-phosphorylated p53. ING2 and p53 also complexed with the histone acetyltransferase p300. ING2 enhanced the interaction between p53 and p300 and acted as a cofactor for p300-mediated p53 acetylation. The level of ING2 expression directly modulated the onset of replicative senescence. While overexpression of ING2 induced senescence in young fibroblasts in a p53-dependent manner, expression of ING2 small interfering RNA delayed the onset of senescence. Hence, ING2 can act as a cofactor of p300 for p53 acetylation and thereby plays a positive regulatory role during p53-mediated replicative senescence. |
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