ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation.
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.
Mesh Terms:
Acetylation, Cell Aging, Cell Division, Cell Line, Cell Proliferation, Homeodomain Proteins, Humans, Nuclear Proteins, Phosphorylation, Protein Processing, Post-Translational, Receptors, Cytoplasmic and Nuclear, Serine, Trans-Activators, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Acetylation, Cell Aging, Cell Division, Cell Line, Cell Proliferation, Homeodomain Proteins, Humans, Nuclear Proteins, Phosphorylation, Protein Processing, Post-Translational, Receptors, Cytoplasmic and Nuclear, Serine, Trans-Activators, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Mol. Cell. Biol.
Date: Aug. 01, 2005
PubMed ID: 16024799
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