Ferreira Joao Vasco, Soares Ana Rosa, Ramalho Jose Silva, Pereira Paulo, Girao Henrique
Center of Ophthalmology and Vision Sciences; Institute for Biomedical Imaging and Life Science (IBILI); Faculty of Medicine; University of Coimbra; Coimbra, Portugal.
CEDOC; Faculty of Medicine, New University of Lisbon; Lisbon; Portugal.
Sci Rep. 2015 May 11;5:10210. doi: 10.1038/srep10210.
Chaperone-Mediated Autophagy is a selective form of autophagy. Recently, the degradation of a newly identified CMA substrate, the HIF1A transcription factor, was found to be regulated by the ubiquitin ligase STUB1. In this study we show, for the first time, that K63 ubiquitination is necessary for CMA degradation of HIF1A in vitro and in vivo. Additionally, STUB1 mediates K63 linked ubiquitination of HIF1A. Our findings add a new regulatory step and increase the specificity of the molecular mechanism involved in CMA degradation of HIF1A, expanding the role of ubiquitination to yet another biological process, since the same mechanism might be applicable to other CMA substrates.
伴侣介导的自噬是一种选择性自噬形式。最近，人们发现一种新鉴定出的CMA底物——HIF1A转录因子的降解受泛素连接酶STUB1调控。在本研究中，我们首次表明，K63泛素化在体外和体内对HIF1A的CMA降解都是必需的。此外，STUB1介导HIF1A的K63连接泛素化。我们的发现增加了一个新的调控步骤，并提高了参与HIF1A的CMA降解的分子机制的特异性，将泛素化的作用扩展到另一个生物学过程，因为相同的机制可能适用于其他CMA底物。
