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.
Pedeux
Remy
R
Laboratory of Human Carcinogenesis, CCR, NCI, NIH, 37 Convent Dr., Bldg 37, Room 3068, Bethesda, MD 20892-4255, USA.
Sengupta
Sagar
S
Shen
Jiang Cheng
JC
Demidov
Oleg N
ON
Saito
Shin'ichi
S
Onogi
Hitoshi
H
Kumamoto
Kensuke
K
Wincovitch
Stephen
S
Garfield
Susan H
SH
McMenamin
Mary
M
Nagashima
Makoto
M
Grossman
Steven R
SR
Appella
Ettore
E
Harris
Curtis C
CC
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*
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