Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65
Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65
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DOI：
10.1074/jbc.m209572200
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发表时间：
2003-01-24
影响因子：
4.8
通讯作者：
Benkirane, M
中科院分区：
文献类型：
--
作者：
Kiernan, R;Brès, V;Benkirane, M
核因子-kappaB是一个真核转录因子家族，参与调节多种细胞基因，参与免疫、急性期和炎症反应的即刻早期过程。核因子-kappaB的细胞定位和转录活性受到其伴侣IkappaBalpha的严格调控。在这里，我们证明了核因子-kappaB的p65亚单位被赖氨酸122和123上的p300和PCAF乙酰化。HDAC2和HDAC3都能与p65相互作用，但只有HDAC3能使p65去乙酰化。P65的乙酰化降低了它与kappaB-DNA的结合能力。最后，p65的乙酰化有助于将其从DNA中移除，从而使其通过IkappaBalpha从细胞核中输出。我们认为p65的乙酰化在IkappaBalpha介导的核因子-kappaB转录活性的减弱中起关键作用，这是恢复诱导后细胞潜伏期的一个重要过程。
NF-kappaB represents a family of eukaryotic transcription factors participating in the regulation of various cellular genes involved in the immediate early processes of immune, acute-phase, and inflammatory responses. Cellular localization and consequently the transcriptional activity of NF-kappaB is tightly regulated by its partner IkappaBalpha. Here, we show that the p65 subunit of NF-kappaB is acetylated by both p300 and PCAF on lysines 122 and 123. Both HDAC2 and HDAC3 interact with p65, although only HDAC3 was able to deacetylate p65. Acetylation of p65 reduces its ability to bind kappaB-DNA. Finally, acetylation of p65 facilitated its removal from DNA and consequently its IkappaBalpha-mediated export from the nucleus. We propose that acetylation of p65 plays a key role in IkappaBalpha-mediated attenuation of NF-kappaB transcriptional activity which is an important process that restores the latent state in post-induced cells.