Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2
Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2
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DOI：
10.1038/ncb1545
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发表时间：
2007-03-01
影响因子：
21.3
通讯作者：
Benkirane, Monsef
中科院分区：
文献类型：
--
作者：
Linares, Laetitia K.;Kiernan, Rosemary;Benkirane, Monsef
p300- cbp相关因子（PCAF）是一种组蛋白乙酰转移酶（HAT），参与多种转录调节因子的可逆乙酰化(1)，包括肿瘤抑制因子p53。它参与许多细胞过程，如转录、分化、增殖和凋亡。我们观察到，在HeLa或U2OS细胞系中敲低PCAF表达可诱导癌蛋白Hdm2的稳定，Hdm2是一种环指E3连接酶，主要以其控制p53稳定性的作用而闻名（2,3）。为了研究这种作用的分子基础，我们研究了PCAF是否参与Hdm2泛素化。在这里，我们发现PCAF除了其乙酰转移酶活性外，还具有内在的泛素化活性，这对于控制Hdm2表达水平至关重要，因此p53具有功能。我们的数据强调了PCAF和Hdm2活性之间的调控串扰，这可能在DNA损伤后p53活性的微妙控制中发挥核心作用。
The p300-CBP-associated factor ( PCAF) is a histone acetyltransferase ( HAT) involved in the reversible acetylation of various transcriptional regulators(1), including the tumour suppressor p53. It is implicated in many cellular processes, such as transcription, differentiation, proliferation and apoptosis. We observed that knockdown of PCAF expression in HeLa or U2OS cell lines induces stabilization of the oncoprotein Hdm2, a RING finger E3 ligase primarily known for its role in controlling p53 stability(2,3). To investigate the molecular basis of this effect, we examined whether PCAF is involved in Hdm2 ubiquitination. Here, we show that PCAF, in addition to its acetyltransferase activity, possesses an intrinsic ubiquitination activity that is critical for controlling Hdm2 expression levels, and thus p53 functions. Our data highlight a regulatory crosstalk between PCAF and Hdm2 activities, which is likely to have a central role in the subtle control of p53 activity after DNA damage.