Regulation of cellular functions and diseases by the MARCH E3 ubiquitin ligases

The membrane-associated RING-CH (MARCH) family is a type of membrane-localized E3 ubiquitin ligases, which catalyze substrate ubiquitination via their characteristic RING-CH domains. MARCH proteins target their substrates for polyubiquitination of different linkage types and degradation via distinct routes. This review outlines recent advancements about the structural features, subcellular localizations, expression profiles of MARCH proteins and their roles in regulation of physiological processes and diseases, such as immune response, organelle homeostasis and tumorigenesis. Future studies would identify additional targets of the MARCH family and reveal the regulatory networks of MARCH family on substrates, offering an opportunity to target the MARCH family for development of drugs against severe human diseases.