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 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.
MeSH terms
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Acetylation
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Amino Acid Sequence
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Apoptosis / drug effects
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Apoptosis / physiology*
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Bleomycin / pharmacology
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Cell Division
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Cells, Cultured / drug effects
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Cells, Cultured / radiation effects
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Cisplatin / pharmacology
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Cloning, Molecular
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DNA Damage*
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Doxorubicin / pharmacology
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Etoposide / pharmacology
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G1 Phase
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Gamma Rays
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Gene Expression Regulation / drug effects
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Homeodomain Proteins / genetics
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Homeodomain Proteins / isolation & purification
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Homeodomain Proteins / physiology*
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Humans
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Molecular Sequence Data
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Protein Processing, Post-Translational*
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Receptors, Cytoplasmic and Nuclear
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Transcription, Genetic
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / radiation effects
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Tumor Stem Cell Assay
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Tumor Suppressor Protein p53 / metabolism*
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Tumor Suppressor Proteins*
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Zinostatin / pharmacology
Substances
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Homeodomain Proteins
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ING2 protein, human
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Receptors, Cytoplasmic and Nuclear
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Bleomycin
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Etoposide
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Doxorubicin
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Zinostatin
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Cisplatin
Associated data
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GENBANK/AF053537
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GENBANK/AF078835