Sanz-Martinez Pablo, Berkane Rayene, Stolz Alexandra
Institute of Biochemistry 2 (IBC2), Goethe University, Frankfurt am Main, Germany.
Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University, Frankfurt am Main, Germany.
Autophagy. 2025 Feb;21(2):480-486. doi: 10.1080/15548627.2024.2395725. Epub 2024 Sep 3.
Selective macroautophagy/autophagy of the endoplasmic reticulum, known as reticulophagy/ER-phagy, is essential to maintain ER homeostasis. We recently showed that members of the autophagy receptor family RETREG/FAM134 are regulated by phosphorylation-dependent ubiquitination. In an unbiased screen we had identified several kinases downstream of MTOR with profound impact on reticulophagy flux, including ATR and CSNK2/CK2. Inhibition of CSNK2 by SGC-CK2-1 prevented regulatory ubiquitination of RETREG1/FAM134B and RETREG3/FAM134C upon autophagy activation as well as the formation of high-density RETREG1- and RETREG3-clusters. Here we report on additional resource data of global proteomics upon CSNK2 and ATR inhibition, respectively. Our data suggests that the function of CSNK2 is mainly limited to the ER/reticulophagy and Golgi/Golgiphagy, while ATR inhibition by VE-822 affects the vast majority of organelles/selective autophagy pathways. ATRi: ATR inhibitor VE-822; CSNK2i: CSNK2 inhibitor SGC-CK2-1; ER: endoplasmic reticulum.
内质网的选择性巨自噬/自噬，即网织自噬/内质网自噬，对于维持内质网稳态至关重要。我们最近发现自噬受体家族RETREG/FAM134的成员受磷酸化依赖性泛素化调控。在一项无偏向性筛选中，我们鉴定出了MTOR下游的几种激酶，它们对网织自噬通量有深远影响，包括ATR和CSNK2/CK2。SGC-CK2-1对CSNK2的抑制作用可防止自噬激活时RETREG1/FAM134B和RETREG3/FAM134C的调节性泛素化，以及高密度RETREG1和RETREG3聚集体的形成。在此，我们分别报告了CSNK2和ATR抑制后全球蛋白质组学的其他资源数据。我们的数据表明，CSNK2的功能主要限于内质网/网织自噬和高尔基体/高尔基体自噬，而VE-822对ATR的抑制作用则影响绝大多数细胞器/选择性自噬途径。ATR抑制剂：ATR抑制剂VE-822；CSNK2抑制剂：CSNK2抑制剂SGC-CK2-1；内质网：endoplasmic reticulum。
