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

doi:10.1073/pnas.161151798

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

^*Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; ^‡Biology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan; and ^§Departments of Biochemistry and Molecular Biology and Oncology, University of Calgary Health Sciences Centre, Calgary, AB, Canada T2N 1N4

Edited by Bert Vogelstein, Johns Hopkins Oncology Center, Baltimore, MD, and approved June 11, 2001 (received for review March 28, 2001)

Abstract

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 G₁-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.

Footnotes

↵ † Present address: Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575, Japan.
↵ ¶ To whom reprint requests should be addressed at: Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Building 37, Room 2C05, Bethesda, MD 20892-4255. E-mail: curtis_harris{at}nih.gov.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF078835 and AF053537).
Abbreviations:

Pingn,

rabbit polyclonal antibodies for p33INGn;

HDAC,

histone deacetylase complex;

ATM,

ataxia-telangiectasia mutated