title: ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation.
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.
authors: Laboratory of Human Carcinogenesis, CCR, NCI, NIH, 37 Convent Dr., Bldg 37, Room 3068, Bethesda, MD 20892-4255, USA.
authors: Remy
authors: R
authors: Pedeux
authors: Sagar
authors: S
authors: Sengupta
authors: Jiang Cheng
authors: JC
authors: Shen
authors: Oleg N
authors: ON
authors: Demidov
authors: Shin'ichi
authors: S
authors: Saito
authors: Hitoshi
authors: H
authors: Onogi
authors: Kensuke
authors: K
authors: Kumamoto
authors: Stephen
authors: S
authors: Wincovitch
authors: Susan H
authors: SH
authors: Garfield
authors: Mary
authors: M
authors: McMenamin
authors: Makoto
authors: M
authors: Nagashima
authors: Steven R
authors: SR
authors: Grossman
authors: Ettore
authors: E
authors: Appella
authors: Curtis C
authors: CC
authors: Harris
mesh_terms: D000107:Acetylation; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000502:physiology*; D012694:Serine / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C444654:ING2 protein, human; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D012694:Serine