TY - JOUR
T1 - MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation
AU - Jin, Yetao
AU - Zeng, Shelya X.
AU - Dai, Mu Shui
AU - Yang, Xiang Jiao
AU - Lu, Hua
PY - 2002/8/23
Y1 - 2002/8/23
N2 - Our previous study shows that MDM2, a negative feed-back regulator of the tumor suppressor p53, inhibits p300-mediated p53 acetylation. Because PCAF (p300/CREB-binding protein-associated factor) also acetylates and activates p53 after DNA damage, in this study we have examined the effect of MDM2 on PCAF-mediated p53 acetylation. We have found that MDM2 inhibited p53 acetylation by PCAF in vitro. In addition, when overexpressed, MDM2 inhibited PCAF-mediated p53 acetylation in cells. MDM2 interacted with PCAF both in vitro and in cells, as assessed using GST fusion protein interaction and immunoprecipitation assays, respectively. Consistent with the above results, MDM2 significantly repressed the activation of p53 transcriptional activity by PCAF without apparently affecting the level of p53. In addition, MDM2 co-resided with p53 at the p53-responsive mdm2 and p21waf1/cip1 promoters, inhibiting expression of the endogenous p21waf1/cip1. These results demonstrate that MDM2 can inhibit PCAF-mediated p53 acetylation and activation.
AB - Our previous study shows that MDM2, a negative feed-back regulator of the tumor suppressor p53, inhibits p300-mediated p53 acetylation. Because PCAF (p300/CREB-binding protein-associated factor) also acetylates and activates p53 after DNA damage, in this study we have examined the effect of MDM2 on PCAF-mediated p53 acetylation. We have found that MDM2 inhibited p53 acetylation by PCAF in vitro. In addition, when overexpressed, MDM2 inhibited PCAF-mediated p53 acetylation in cells. MDM2 interacted with PCAF both in vitro and in cells, as assessed using GST fusion protein interaction and immunoprecipitation assays, respectively. Consistent with the above results, MDM2 significantly repressed the activation of p53 transcriptional activity by PCAF without apparently affecting the level of p53. In addition, MDM2 co-resided with p53 at the p53-responsive mdm2 and p21waf1/cip1 promoters, inhibiting expression of the endogenous p21waf1/cip1. These results demonstrate that MDM2 can inhibit PCAF-mediated p53 acetylation and activation.
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U2 - 10.1074/jbc.M204078200
DO - 10.1074/jbc.M204078200
M3 - Article
C2 - 12068014
AN - SCOPUS:0037163085
SN - 0021-9258
VL - 277
SP - 30838
EP - 30843
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 34
ER -