Acetylation regulates transcription factor activity at multiple levels
Acetylation regulates transcription factor activity at multiple levels
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DOI：
10.1016/s1097-2765(00)80253-1
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发表时间：
2000-04-01
期刊：
影响因子：
16
通讯作者：
Talianidis, I
中科院分区：
文献类型：
--
作者：
Soutoglou, E;Katrakili, N;Talianidis, I
CREB结合蛋白(CBP)具有内源性的乙酰转移酶活性，能够乙酰化核小体组蛋白和几种非组蛋白。在这里，研究表明，CBP可以乙酰化核激素受体家族的成员肝细胞核因子-4(HNF-4)在核定位序列中的赖氨酸残基。CBP介导的乙酰化对于HNF-4的适当核保留至关重要，否则HNF-4通过CRM1途径运输到细胞质。乙酰化还增加了HNF-4DNA结合活性及其与CBP本身相互作用的亲和力，这是靶基因激活所必需的。结果表明，乙酰化是一种关键的翻译后修饰，可能会影响转录因子的几个性质，对其生物学功能的执行至关重要。
CREB-binding protein (CBP) possesses an intrinsic acetyltransferase activity capable of acetylating nucleosomal histones as well as several nonhistone proteins. Here, it is shown that CBP can acetylate hepatocyte nuclear factor-4 (HNF-4), a member of the nuclear hormone receptor family, at lysine residues within the nuclear localization sequence. CBP-mediated acetylation is crucial for the proper nuclear retention of HNF-4, which is otherwise transported out to the cytoplasm via the CRM1 pathway. Acetylation also increases HNF-4 DNA binding activity and its affinity of interaction with CBP itself and is required for target gene activation. The results show that acetylation is a key posttranslational modification that may affect several properties of a transcription factor critical for the execution of its biological functions.