Roach Tiffany G, Lång Heljä K M, Xiong Wen, Ryhänen Samppa J, Capelluto Daniel G S
Protein Signaling Domains Laboratory, Department of Biological Sciences, Fralin Life Sciences Institute, and Center for Soft Matter and Biological Physics, Virginia Tech, Blacksburg, VA, United States.
Division of Hematology, Oncology, and Stem Cell Transplantation, Children's Hospital, and Pediatric Research Center, The New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Front Cell Dev Biol. 2021 Feb 26;9:643769. doi: 10.3389/fcell.2021.643769. eCollection 2021.
Lysosomal degradation of ubiquitinated transmembrane protein receptors (cargo) relies on the function of Endosomal Sorting Complex Required for Transport (ESCRT) protein complexes. The ESCRT machinery is comprised of five unique oligomeric complexes with distinct functions. Target of Myb1 (TOM1) is an ESCRT protein involved in the initial steps of endosomal cargo sorting. To exert its function, TOM1 associates with ubiquitin moieties on the cargo its VHS and GAT domains. Several ESCRT proteins, including TOLLIP, Endofin, and Hrs, have been reported to form a complex with TOM1 at early endosomal membrane surfaces, which may potentiate the role of TOM1 in cargo sorting. More recently, it was found that TOM1 is involved in other physiological processes, including autophagy, immune responses, and neuroinflammation, which crosstalk with its endosomal cargo sorting function. Alteration of TOM1 function has emerged as a phosphoinositide-dependent survival mechanism for bacterial infections and cancer progression. Based on current knowledge of TOM1-dependent cellular processes, this review illustrates how TOM1 functions in coordination with an array of protein partners under physiological and pathological scenarios.
泛素化跨膜蛋白受体（货物）的溶酶体降解依赖于运输所需内体分选复合体（ESCRT）蛋白复合体的功能。ESCRT机制由五个具有不同功能的独特寡聚复合体组成。Myb1靶蛋白（TOM1）是一种参与内体货物分选初始步骤的ESCRT蛋白。为发挥其功能，TOM1通过其VHS和GAT结构域与货物上的泛素部分结合。据报道，包括Toll相互作用蛋白（TOLLIP）、内吞素（Endofin）和肝细胞生长因子调节酪氨酸激酶底物（Hrs）在内的几种ESCRT蛋白在早期内体膜表面与TOM1形成复合体，这可能增强TOM1在货物分选中的作用。最近发现，TOM1还参与其他生理过程，包括自噬、免疫反应和神经炎症，这些过程与其内体货物分选功能相互影响。TOM1功能的改变已成为细菌感染和癌症进展中磷酸肌醇依赖性的生存机制。基于目前对TOM1依赖性细胞过程的了解，本综述阐述了TOM1在生理和病理情况下如何与一系列蛋白质伙伴协同发挥作用。
