Metabolic stress regulates basic transcription through acetyl-coenzyme A
Metabolic stress regulates basic transcription through acetyl-coenzyme A
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DOI：
10.1007/s00018-005-4516-6
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发表时间：
2005-03-01
影响因子：
8
通讯作者：
Usheva, A
中科院分区：
文献类型：
--
作者：
Choi, CH;Zimon, A;Usheva, A
最近已证明一般转录因子的乙酰化和自乙酰化，但这些修饰的功能意义尚不清楚。乙酰辅酶 A 的存在会激活基础转录，并且转录因子 IIB (TFIB) 的乙酰化已被证明可以在多种情况下激活转录。如果自身乙酰化是真核生物中的重要途径，那么乙酰辅酶 A 的调控途径在转录调控中也应该很重要。禁食代表一种急性代谢应激，它会提高乙酰辅酶 A 的水平，而线粒体老化则代表一种累积压力。我们发现，小鼠禁食后乙酰化 TFIIB 的组织特异性水平发生显着变化，这表明代谢在转录的直接调节中发挥着作用。我们还观察到，与年轻小鼠相比，老年小鼠组织中乙酰基-TFIIB 大幅增加。 Sir2 家族脱乙酰酶负责调节乙酰辅酶 A 的合成，最近已被证明可以通过与热量限制相关的途径赋予多种生物体长寿。我们假设蛋白质乙酰化和 Sir2 相关的脱乙酰化可能通过乙酰辅酶 A 对关键转录因子和转录调节因子的可用性和作用与转录的代谢调节有关。
The acetylation and auto-acetylation of general transcription factors has recently been demonstrated, but the functional significance of these modifications is unclear. The presence of acetyl-coenzyme A activates basal transcription, and acetylation of transcription factor IIB ( TFIIB) has been shown to activate transcription in several contexts. If auto-acetylation is an important pathway in eukaryotes, the regulatory pathways for acetyl-coenzyme A should be important in transcription regulation. Fasting represents an acute metabolic stress which should elevate levels of acetyl-coenzyme A, while mitochondrial aging represents a cumulative stress. We show that tissue-specific levels of acetylated TFIIB change dramatically in response to fasting in mice, suggesting a role for metabolism in the direct regulation of transcription. We also observed a large increase in acetyl-TFIIB in tissues from aged mice relative to younger mice. Sir2 family deacetylases, which regulate acetyl-coenzyme A synthesis, have recently been shown to impart longevity in a variety of organisms through a pathway related to calorie restriction. We hypothesize that protein acetylation and Sir2-related deacetylation may be tied to the metabolic regulation of transcription through the availability and action of acetyl-coenzyme A on key transcription factors and transcriptional regulators.