Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Mol Cell. 2015 Jun 4;58(5):755-66. doi: 10.1016/j.molcel.2015.04.012. Epub 2015 May 7.
Protein function is often regulated and controlled by posttranslational modifications, such as oxidation. Although oxidation has been mainly considered to be uncontrolled and nonenzymatic, many enzymatic oxidations occur on enzyme-selected lysine residues; for instance, LOXL2 oxidizes lysines by converting the ε-amino groups into aldehyde groups. Using an unbiased proteomic approach, we have identified methylated TAF10, a member of the TFIID complex, as a LOXL2 substrate. LOXL2 oxidation of TAF10 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. In embryonic stem cells, this results in the inactivation of the pluripotency genes and loss of the pluripotent capacity. During zebrafish development, the absence of LOXL2 resulted in the aberrant overexpression of the neural progenitor gene Sox2 and impaired neural differentiation. Thus, lysine oxidation of the transcription factor TAF10 is a controlled protein modification and demonstrates a role for protein oxidation in regulating pluripotency genes.
蛋白质的功能通常受到翻译后修饰的调节和控制，如氧化。虽然氧化主要被认为是不可控和非酶促的，但许多酶促氧化发生在酶选择的赖氨酸残基上；例如，LOXL2 通过将 ε-氨基转化为醛基来氧化赖氨酸。使用无偏蛋白质组学方法，我们已经鉴定出 TFIID 复合物的成员甲基化 TAF10 是 LOXL2 的底物。LOXL2 对 TAF10 的氧化诱导其从启动子上释放，导致 TFIID 依赖性基因转录受阻。在胚胎干细胞中，这导致多能性基因失活和多能性丧失。在斑马鱼发育过程中，LOXL2 的缺失导致神经祖细胞基因 Sox2 的异常过表达和神经分化受损。因此，转录因子 TAF10 的赖氨酸氧化是一种受控制的蛋白质修饰，并证明了蛋白质氧化在调节多能性基因中的作用。
