PNAS：刘文教授课题组发文分子伴侣参与蛋白质折叠和质量控制的

PNAS：刘文教授课题组发文分子伴侣参与蛋白质折叠和质量控制的HSP70蛋白的新功能

近日，厦门大学药学院“青年千人”刘文教授课题组在《美国科学院院报》(PNAS，IF 9.809)上发表题为Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation的研究论文，揭示了一向以分子伴侣参与蛋白质折叠和质量控制的HSP70蛋白的新功能，同时拓展了组蛋白甲基转移酶PRMT4与去甲基化酶JMJD6的非组蛋白底物的研究领域。该发现是基因转录调控领域的一个大突破，为疾病在基因水平上的治疗提供了理论依据。

原文链接：

Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation.

原文摘要：Although "histone" methyltransferases and demethylases are well established to regulate transcriptional programs and to use nonhistone proteins as substrates, their possible roles in regulation of heat-shock proteins in the nucleus have not been investigated. Here, we report that a highly conserved arginine residue, R469, in HSP70 (heat-shock protein of 70 kDa) proteins, an evolutionarily conserved protein family of ATP-dependent molecular chaperone, was monomethylated (me1), at least partially, by coactivator-associated arginine methyltransferase 1/protein arginine methyltransferase 4 (CARM1/PRMT4) and demethylated by jumonji-domain-containing 6 (JMJD6), both in vitro and in cultured cells. Functional studies revealed that HSP70 could directly regulate retinoid acid (RA)-induced retinoid acid receptor β2 (RARβ2) gene transcription through its binding to chromatin, with R469me1 being essential in this process. HSP70's function in gene transcriptional regulation appears to be distinct from its protein chaperon activity. R469me1 was shown to mediate the interaction between HSP70 and TFIIH, which involves in RNA polymerase II phosphorylation and thus transcriptional initiation. Our findings expand the repertoire of nonhistone substrates targeted by PRMT4 and JMJD6, and reveal a new function of HSP70 proteins in gene transcription at the chromatin level aside from its classic role in protein folding and quality control.

DOI: 10.1073/PNAS.1509658112

作者：阳光森林