An infection-activated redox switch in the lysosomal protease legumain promotes tumor growth
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ABSTRACT: Oxidative stress is a hallmark of tumorigenic infections, yet the underlying oxidation events that contribute to tumor growth remain poorly understood. By using chemical proteomics to map cysteine reactivity in human gastric cells, we determined that infection with the cancer-causing bacterium Helicobacter pylori induces oxidation of the lysosomal protease legumain at Cys219. The site-specific loss of Cys219 reactivity dysregulates intracellular legumain processing and localization in H. pylori-infected cells and increases tumor growth and mortality in a xenograft model. These findings establish a link between cysteine oxidation and tumorigenic signaling during bacterial infection and underscore the importance of oxidative post-translational modifications in tumor growth.
INSTRUMENT(S): LTQ Orbitrap
ORGANISM(S): Homo Sapiens (human) Helicobacter Pylori J99 (campylobacter Pylori J99)
TISSUE(S): Gastric Adenocarcinoma Cell
DISEASE(S): Gastric Adenocarcinoma
SUBMITTER: Daniel Bak
LAB HEAD: Eranthie Weerapana
PROVIDER: PXD025841 | Pride | 2022-03-21
REPOSITORIES: Pride
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