TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: From muscular dystrophy to tumours

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• 作者：Elisa Lazzari ; Germana Meroni ; ^{gmeroni@units.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TRIM ; tripartite motif ; RING ; really interesting new gene ; NHL ; NCL-1 ; HT2A and lin-41 ; LGMD ; limb-girdle muscular dystrophy ; XIAP ; X-linked inhibitor of apoptosis ; PIAS ; protein inhibitor of activated STAT ; NDRG2 ; N-myc downstream regulated gene 2 ; Abi2 ; Abl interactor 2 ; RARα ; retinoic acid receptor alpha ; MuRF1 ; muscle RING finger 1 ; STM ; sarcotubular myopathy ; HEK ; human embryonic kidney ; SUMO ; smallubiquitin-like modifier ; TNFα ; tumor necrosis factor alpha ; NFκB ; nuclear factor kappa B
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：79
• 期：Complete
• 页码：469-477
• 全文大小：972 K

文摘

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.