Ku70 senses cytosolic DNA and assembles a tumor-suppressive signalosome.

ABSTRACT: The innate immune response contributes to the development or attenuation of acute and chronic diseases, including cancer. Microbial DNA and mislocalized DNA from damaged host cells can activate different host responses that shape disease outcomes. Here, we show that mice and humans lacking a single allele of the DNA repair protein Ku70 had increased susceptibility to the development of intestinal cancer. Mechanistically, Ku70 translocates from the nucleus into the cytoplasm where it binds to cytosolic DNA and interacts with the GTPase Ras and the kinase Raf, forming a tripartite protein complex and docking at Rab5⁺Rab7⁺ early-late endosomes. This Ku70-Ras-Raf signalosome activates the MEK-ERK pathways, leading to impaired activation of cell cycle proteins Cdc25A and C

SUBMITTER: Pandey A 

PROVIDER: S-EPMC10816715 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature