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DNA damage-inducible gene p33ING2 negatively regulates cell proliferat…
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.
p33ING1
PHD-finger
apoptosis
cell cycle
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@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
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@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