Vitamin B6 conjugation to nuclear corepressor RIP140 and its role in gene regulation
Vitamin B6 conjugation to nuclear corepressor RIP140 and its role in gene regulation
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DOI：
10.1038/nchembio861
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发表时间：
2007-03-01
影响因子：
14.8
通讯作者：
Wei, Li-Na
中科院分区：
文献类型：
--
作者：
Huq, M. D. Mostaqul;Tsai, Nien-Pei;Wei, Li-Na
吡哆醛5 '-磷酸（PLP），维生素B6的生物活性形式，是氨基酸代谢的重要辅助因子（1），补充维生素B6在许多疾病中具有保护作用（2-5）。除了作为辅因子，它还可以调节类固醇激素受体（6-9）和转录因子（10）的活性。然而，这种调节的分子基础尚不清楚。在这里，我们报告，小鼠核受体相互作用蛋白140（RIP 140）可以通过PLP缀合修饰。通过LC-ESI-MS/MS分析，我们将修饰位点定位到Lys 613。这种修饰增强了其转录辅抑制活性及其在脂肪细胞分化中的生理功能。我们将这种效应归因于RIP 140与组蛋白去乙酰化酶的相互作用增加以及RIP 140的核保留。这项研究揭示了维生素B6在基因调控中的一种新的生理作用，即通过PLP与转录辅助调节因子结合，这代表了一种旧形式的蛋白质翻译后修饰的新功能，具有重要的生物学后果。
Pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, is an important cofactor in amino acid metabolism(1), and supplementary vitamin B6 has protective effects in many disorders(2-5). Other than serving as a cofactor, it can also modulate the activities of steroid hormone receptors(6-9) and transcription factors(10). However, the molecular basis of this modulation is unclear. Here, we report that mouse nuclear receptor interacting protein 140 (RIP140) can be modified by PLP conjugation. We mapped the modification site to Lys613 by LC-ESI-MS/MS analysis. This modification enhanced its transcriptional corepressive activity and its physiological function in adipocyte differentiation. We attribute this effect to increased interaction of RIP140 with histone deacetylases and nuclear retention of RIP140. This study uncovers a new physiological role of vitamin B6 in gene regulation by PLP conjugation to a transcriptional coregulator, which represents a new function of an old form(11) of protein post-translational modification that has important biological consequences.