TY - JOUR
T1 - The acetylase activity of p300 is dispensable for MDM2 stabilization
AU - Zeng, Shelya X.
AU - Jin, Yetao
AU - Kuninger, David T.
AU - Rotwein, Peter
AU - Lu, Hua
PY - 2003/2/28
Y1 - 2003/2/28
N2 - It has been shown that p300 binds to NMM2 and leads to down-regulation of the p53 function. However, it remains unclear whether the acetylase activity of p300 is necessary for regulating NMM2 stability. In this study, we address this issue. First, p300 did not acetylate NMM2 in solution and in cells. Second, overexpression of p300 in cells increased the level of the NMM2 protein but not its mRNA. Similarly, the acetylase-defective p300 AT2 mutant stabilized the NMM2 protein as well. Consistently, the deacetylase inhibitor, trichostatin A, did not significantly affect the half-life of the endogenous NMM2 protein, whereas p300 enhanced the half-life of NMM2. Finally, both wild type and acetylase-defective mutant p300 proteins associated with NMM2 in nuclear body-like structures where NMM2 might be protected from proteasomal degradation. Thus, these results suggest that p300 appears to stabilize NMM2 by retaining this protein in a specific nuclear structure rather than by acetylating it.
AB - It has been shown that p300 binds to NMM2 and leads to down-regulation of the p53 function. However, it remains unclear whether the acetylase activity of p300 is necessary for regulating NMM2 stability. In this study, we address this issue. First, p300 did not acetylate NMM2 in solution and in cells. Second, overexpression of p300 in cells increased the level of the NMM2 protein but not its mRNA. Similarly, the acetylase-defective p300 AT2 mutant stabilized the NMM2 protein as well. Consistently, the deacetylase inhibitor, trichostatin A, did not significantly affect the half-life of the endogenous NMM2 protein, whereas p300 enhanced the half-life of NMM2. Finally, both wild type and acetylase-defective mutant p300 proteins associated with NMM2 in nuclear body-like structures where NMM2 might be protected from proteasomal degradation. Thus, these results suggest that p300 appears to stabilize NMM2 by retaining this protein in a specific nuclear structure rather than by acetylating it.
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U2 - 10.1074/jbc.M209030200
DO - 10.1074/jbc.M209030200
M3 - Article
C2 - 12493762
AN - SCOPUS:0037470040
SN - 0021-9258
VL - 278
SP - 7453
EP - 7458
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 9
ER -