Wang Zhenda, Hu Jia, Li Ge, Qu Liujing, He Qihua, Lou Yaxin, Song Quansheng, Ma Dalong, Chen Yingyu
a Key Laboratory of Medical Immunology; Ministry of Health ; Peking University Health Science Center ; Beijing , China.
Autophagy. 2014;10(12):2158-70. doi: 10.4161/auto.36439.
Autophagy is a multistep process that involves the degradation and digestion of intracellular components by the lysosome. It has been proved that many core autophagy-related molecules participate in this event. However, new component proteins that regulate autophagy are still being discovered. At present, we report PHF23 (PHD finger protein 23) with a PHD-like zinc finger domain that can negatively regulate autophagy. Data from experiments indicated that the overexpression of PHF23 impaired autophagy, as characterized by decreased levels of LC3B-II and weakened degradation of endogenous and exogenous autophagic substrates. Conversely, knockdown of PHF23 resulted in opposite effects. Molecular mechanism studies suggested that PHF23 interacts with LRSAM1, which is an E3 ligase key for ubiquitin-dependent autophagy against invading bacteria. PHF23 promotes the ubiquitination and proteasome degradation of LRSAM1. We also show that the PHD finger of PHF23 is a functional domain needed for the interaction with LRSAM1. Altogether, our results indicate that PHF23 is a negative regulator associated in autophagy via the LRSAM1 signaling pathway. The physical and functional connection between the PHF23 and LRSAM1 needs further investigation.
自噬是一个多步骤过程，涉及溶酶体对细胞内成分的降解和消化。已证实许多核心自噬相关分子参与此过程。然而，仍在不断发现调节自噬的新组成蛋白。目前，我们报道了具有类PHD锌指结构域的PHF23（PHD指蛋白23），它可负向调节自噬。实验数据表明，PHF23的过表达会损害自噬，其特征是LC3B-II水平降低以及内源性和外源性自噬底物的降解减弱。相反，敲低PHF23会产生相反的效果。分子机制研究表明，PHF23与LRSAM1相互作用，LRSAM1是一种E3连接酶，对依赖泛素的抗入侵细菌自噬起关键作用。PHF23促进LRSAM1的泛素化和蛋白酶体降解。我们还表明，PHF23的PHD指是与LRSAM1相互作用所需的功能结构域。总之，我们的结果表明，PHF23是通过LRSAM1信号通路参与自噬的负调节因子。PHF23与LRSAM1之间的物理和功能联系需要进一步研究。
