DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53.
The p33ING1 protein is a regulator of cell cycle, senescence, and apoptosis. Three alternatively spliced transcripts of p33ING1 encode p47ING1a, p33ING1b, and p24ING1c. We cloned an additional ING family member, p33ING2/ING1L. Unlike p33ING1b, p33ING2 is induced by the DNA-damaging agents etoposide and neocarzinostatin. p33ING1b and p33ING2 negatively regulate cell growth and survival in a p53-dependent manner through induction of G(1)-phase cell-cycle arrest and apoptosis. p33ING2 strongly enhances the transcriptional-transactivation activity of p53. Furthermore, p33ING2 expression increases the acetylation of p53 at Lys-382. Taken together, p33ING2 is a DNA damage-inducible gene that negatively regulates cell proliferation through activation of p53 by enhancing its acetylation.
Nagashima
M
M
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shiseki
M
M
Miura
K
K
Hagiwara
K
K
Linke
S P
SP
Pedeux
R
R
Wang
X W
XW
Yokota
J
J
Riabowol
K
K
Harris
C C
CC
D000107:Acetylation; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001761:Bleomycin / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology; D003001:Cloning, Molecular; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D016193:G1 Phase; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D009353:Zinostatin / Q000494:pharmacology
D018398:Homeodomain Proteins; C444654:ING2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D001761:Bleomycin; D005047:Etoposide; D004317:Doxorubicin; D009353:Zinostatin; D002945:Cisplatin