MARCH2/3 target FcγRI for K27-linked polyubiquitination and degradation to restrict the inflammatory response.
MARCH2 and MARCH3 redundantly target FcγRI for K27-linked polyubiquitination and degradation, limiting inflammatory responses and disease severity.
- Why it matters: Understanding how FcγRI is regulated post-translationally is crucial because its activity influences immune responses and inflammation, yet this regulation remains unclear.
- What they did: The study used genetic knockout models and molecular assays to show that MARCH2 and MARCH3 associate with FcγRI, mediating its K27-linked polyubiquitination at specific lysines, leading to lysosomal degradation.
- The result: Loss of MARCH2/3 increases FcγRI levels and amplifies inflammatory gene transcription, worsening inflammation and disease in mice, highlighting these ligases as key regulators of immune homeostasis.