The deubiquitinase USP38 affects cellular functions through interacting with LSD1.

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Deubiquitination is a crucial posttranslational modification in mammalian cells.
• Deubiquitinases (DUBs) regulate protein function by removing ubiquitin chains.
• The role of USP38 in modulating LSD1 protein and cellular physiology was examined.

Purpose of the Study:

• To investigate the specific deubiquitinase activity of USP38 on the LSD1 protein.
• To elucidate how USP38 influences LSD1 stability and protein interactions.
• To determine the impact of USP38-LSD1 interaction on cellular functions, including proliferation and drug response.

Main Methods:

• Western blotting and immunoprecipitation were used to analyze protein stability and interactions.
• Real-time quantitative PCR and luciferase reporter assays assessed gene expression and activity.
• Cell proliferation, colony formation, and drug treatment assays evaluated cellular phenotypes.

Main Results:

• USP38 directly binds to LSD1 and removes its ubiquitin chain, preventing proteasomal degradation and stabilizing LSD1.
• USP38 enhances LSD1's ability to activate signaling pathways, promoting cell proliferation and colony formation.
• USP38 increases the drug tolerance of human colon cancer cells.

Conclusions:

• USP38 functions as an LSD1-specific deubiquitinase.
• USP38 modulates cellular physiology, including proliferation and drug resistance, via its interaction with LSD1.