E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP-1 Proteasomal Degradation.

ABSTRACT: As a highly organized system, endo-lysosomes play a crucial role in maintaining immune homeostasis. However, the mechanisms involved in regulating endo-lysosome progression and subsequent inflammatory responses are not fully understood. By screening 103 E3 ubiquitin ligases in regulating endo-lysosomal acidification, it is discovered that lysosomal RNF13 inhibits lysosome maturation and promotes inflammatory responses mediated by endosomal Toll-like receptors (TLRs) in macrophages. Mechanistically, RNF13 mediates K48-linked polyubiquitination of LAMP-1 at residue K128 for proteasomal degradation. Upon TLRs activation, LAMP-1 promotes lysosomes maturation, which accelerates lysosomal degradation of TLRs and reduces TLR signaling in macrophages. Furthermore, peripheral blood mononuclear cell

SUBMITTER: Liu W 

PROVIDER: S-EPMC11348240 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature