Circadian clock control by SUMOylation of BMAL1
Circadian clock control by SUMOylation of BMAL1
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DOI：
10.1126/science.1110689
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发表时间：
2005-08-26
期刊：
影响因子：
56.9
通讯作者：
Sassone-Corsi, P
中科院分区：
文献类型：
--
作者：
Cardone, L;Hirayamna, J;Sassone-Corsi, P
控制昼夜节律的分子机制是基于在调节反馈回路中组织的时钟蛋白。尽管对时钟蛋白的转化后修饰可能会很好地控制其昼夜节律功能，但迄今为止可获得的信息有限。在这里，我们发现BMAL1是生物钟机制的重要转录因子组成部分，在体内被高度保守的赖氨酸残基（Lys(259)） sumoylation。BMAL1显示出与它在小鼠肝脏中的激活相似的sumo化的昼夜节律模式。BMAL1的summoylation需要并由CLOCK （BMAL1的异源二聚化伙伴）诱导。sumo缺陷BMAL1的异位表达表明，sumo化在BMAL1昼夜节律表达和生物钟节律中起重要作用。这揭示了生物钟核心机制内的额外调节水平。
The molecular machinery that governs circadian rhythmicity is based on clock proteins organized in regulatory feedback loops. Although posttranstational modification of clock proteins is likely to finely control their circadian functions, only limited information is available to date. Here, we show that BMAL1, an essential transcription factor component of-the clock mechanism, is SUMOylated on a highly conserved lysine residue (Lys(259)) in vivo. BMAL1 shows a circadian pattern of SUMOylation that parallels its activation in the mouse liver. SUMOylation of BMAL1 requires and is induced by CLOCK, the heterodimerization partner of BMAL1. Ectopic expression of a SUMO-deficient BMAL1 demonstrates that SUMOylation plays an important role in BMAL1 circadian expression and clock rhythmicity. This reveals an additional level of regulation within the core mechanism of the circadian clock.