title: Overview of the membrane-associated RING-CH (MARCH) E3 ligase family.
abstract: E3 ligases are critical checkpoints for protein ubiquitination, a signal that often results in protein sorting and degradation but has also been linked to regulation of transcription and DNA repair. In line with their key role in cellular trafficking and cell-cycle control, malfunction of E3 ligases is often linked to human disease. Thus, they have emerged as prime drug targets. However, the molecular basis of action of membrane-bound E3 ligases is still unknown. Here, we review the current knowledge on the membrane-embedded MARCH E3 ligases (MARCH-1-6,7,8,11) with a focus on how the transmembrane regions can contribute via GxxxG-motifs to the selection and recognition of other membrane proteins as substrates for ubiquitination. Further understanding of the molecular parameters that govern target protein recognition of MARCH E3 ligases will contribute to development of strategies for therapeutic regulation of MARCH-induced ubiquitination.
authors.affiliation: Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership University of Oslo, N-0349 Oslo, Norway.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Department of Biosciences, Centre for Immune Regulation, University of Oslo, N-0316 Oslo, Norway.
authors.forename: Oddmund
authors.initials: O
authors.lastname: Bakke
authors.affiliation: Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership University of Oslo, N-0349 Oslo, Norway; Institute for Experimental Medical Research, Oslo University Hospital, N-0424 Oslo, Norway. Electronic address: j.p.morth@ncmm.uio.no.
authors.forename: J Preben
authors.initials: JP
authors.lastname: Morth
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D005810:Multigene Family; D010802:Phylogeny; D055503:Protein Multimerization; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D044767:Ubiquitin-Protein Ligases
keywords: GxxxG; MARCH E3 ligase; MARCH-1; MHC-II; Ubiquitination