Abstract
p53 functions as a central node for organizing whether the cell responds to stress with apoptosis or cell cycle arrest; however, the molecular events that lead to apoptotic responses are not completely understood. Here, we identified p90 (also called Coiled-Coil Domain Containing 8) as a unique regulator for p53. p90 has no obvious effects on either the levels of p53 or p53-mediated cell cycle arrest but is specifically required for p53-mediated apoptosis upon DNA damage. Notably, p90 is crucial for Tip60-dependent p53 acetylation at Lys120, therefore facilitating activation of the proapoptotic targets. These studies indicate that p90 is a critical cofactor for p53-mediated apoptosis through promoting Tip60-mediated p53 acetylation.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Amino Acid Sequence
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Apoptosis / genetics*
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Base Sequence
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Blotting, Western
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Checkpoints / drug effects*
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Cell Cycle Checkpoints / genetics*
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Cell Line
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DNA Damage*
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Histone Acetyltransferases / metabolism*
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Humans
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Immunoprecipitation
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Lysine Acetyltransferase 5
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Molecular Sequence Data
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism*
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Oligonucleotides / genetics
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RNA Interference
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Sequence Analysis, DNA
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Tumor Suppressor Protein p53 / metabolism*
Substances
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CCDC8 protein, human
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Carrier Proteins
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Multiprotein Complexes
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Oligonucleotides
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Tumor Suppressor Protein p53
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Histone Acetyltransferases
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KAT5 protein, human
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Lysine Acetyltransferase 5