title: TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: From muscular dystrophy to tumours.
abstract: TRIM32 is a member of the TRIpartite Motif family characterised by the presence of an N-terminal three-domain-module that includes a RING domain, which confers E3 ubiquitin ligase activity, one or two B-box domains and a Coiled-Coil region that mediates oligomerisation. Several TRIM32 substrates were identified including muscular proteins and proteins involved in cell cycle regulation and cell motility. As ubiquitination is a versatile post-translational modification that can affect target turnover, sub-cellular localisation or activity, it is likely that diverse substrates may be differentially affected by TRIM32-mediated ubiquitination, reflecting its multi-faceted roles in muscle physiology, cancer and immunity. With particular relevance for muscle physiology, mutations in TRIM32 are associated with autosomal recessive Limb-Girdle Muscular Dystrophy 2H, a muscle-wasting disease with variable clinical spectrum ranging from almost asymptomatic to wheelchair-bound patients. In this review, we will focus on the ability of TRIM32 to mark specific substrates for proteasomal degradation discussing how the TRIM32-proteasome axis may (i) be important for muscle homeostasis and for the pathogenesis of muscular dystrophy; and (ii) define either an oncogenic or tumour suppressive role for TRIM32 in the context of different types of cancer.
authors.affiliation: Department of Life Sciences, University of Trieste and Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lazzari
authors.affiliation: Department of Life Sciences, University of Trieste and Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. Electronic address: gmeroni@units.it.
authors.forename: Germana
authors.initials: G
authors.lastname: Meroni
mesh_terms: D000818:Animals; D006801:Humans; D009132:Muscles / Q000201:enzymology / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000503:physiopathology; D009369:Neoplasms / Q000201:enzymology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D044767:Ubiquitin-Protein Ligases
keywords: Cancer; Muscle physiology and regeneration; Proteasome; TRIM; Ubiquitin E3 ligases