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DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53

2001; National Academy of Sciences; Volume: 98; Issue: 17 Linguagem: Inglês

10.1073/pnas.161151798

1091-6490

Makoto Nagashima, Masayuki Shiseki, Koh Miura, Koichi Hagiwara, Steven P. Linke, Rémy Pedeux, Xin Wei Wang, Jun Yokota, Karl Riabowol, Curtis C. Harris,

Ubiquitin and proteasome pathways

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.