Lysine acetylation and the bromodomain: a new partnership for signaling
Lysine acetylation and the bromodomain: a new partnership for signaling
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DOI：
10.1002/bies.20104
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发表时间：
2004-10
期刊：
影响因子：
4
通讯作者：
Xiang-Jiao Yang
中科院分区：
文献类型：
--
作者：
Xiang-Jiao Yang
赖氨酸乙酰化已被证明存在于许多蛋白质靶标中，包括核心组蛋白、大约40个转录因子和30多个其他蛋白质。这种修饰在体内是可逆的，其特异性和水平在很大程度上受信号依赖的底物与乙酰基转移酶和脱乙酰酶的结合控制。与其他共价修饰一样，赖氨酸乙酰化通过“功能丧失”和“功能获得”机制发挥作用。在后者中，赖氨酸乙酰化为溴域蛋白产生特定的对接位点。例如，Gcn5、PCAF、TAF1和CBP的溴结构域能够识别组蛋白、HIV Tat、P53、c-Myb或MyoD中的乙酰赖氨酸残基。除了乙酰赖氨酸部分，侧翼序列也有助于有效识别。乙酰赖氨酸和溴域之间的关系使人想起磷酸特异性结合模块对磷酸化残基的特异性识别，如SH2结构域和14-3-3蛋白。因此，赖氨酸乙酰化与溴结构域形成了一种新的信号伙伴关系，以调控体内蛋白质功能的时间和空间调节。《生物文集》26：1076-1087,2004。©2004威利期刊公司。
Lysine acetylation has been shown to occur in many protein targets, including core histones, about 40 transcription factors and over 30 other proteins. This modification is reversible in vivo, with its specificity and level being largely controlled by signal‐dependent association of substrates with acetyltransferases and deacetylases. Like other covalent modifications, lysine acetylation exerts its effects through “loss‐of‐function” and “gain‐of‐function” mechanisms. Among the latter, lysine acetylation generates specific docking sites for bromodomain proteins. For example, bromodomains of Gcn5, PCAF, TAF1 and CBP are able to recognize acetyllysine residues in histones, HIV Tat, p53, c‐Myb or MyoD. In addition to the acetyllysine moiety, the flanking sequences also contribute to efficient recognition. The relationship between acetyllysine and bromodomains is reminiscent of the specific recognition of phosphorylated residues by phospho‐specific binding modules such as SH2 domains and 14‐3‐3 proteins. Therefore, lysine acetylation forges a novel signaling partnership with bromodomains to govern the temporal and spatial regulation of protein functions in vivo. BioEssays 26:1076–1087, 2004. © 2004 Wiley Periodicals, Inc.