Abstract
TRIpartite motif (TRIM) proteins are part of the largest subfamilies of E3 ligases that mediate the transfer of ubiquitin to substrate target proteins. In this review, we focus on TRIM37 in the normal cell and in pathological conditions, with an emphasis on the MULIBREY (MUscle-LIver-BRain-EYe) genetic disorder caused by TRIM37 mutations. TRIM37 is characterized by the presence of a RING domain, B-box motifs, and a coiled-coil region, and its C-terminal part includes the MATH domain specific to TRIM37. MULIBREY nanism is a rare autosomal recessive caused by TRIM37 mutations and characterized by severe pre- and postnatal growth failure. Constrictive pericarditis is the most serious anomaly of the disease and is present in about 20% of patients. The patients have a deregulation of glucose and lipid metabolism, including type 2 diabetes, fatty liver, and hypertension. Puzzlingly, MULIBREY patients, deficient for TRIM37, are plagued with numerous tumors. Among non-MULIBREY patients affected by cancer, a wide variety of cancers are associated with an overexpression of TRIM37. This suggests that normal cells need an optimal equilibrium in TRIM37 expression. Finding a way to keep that balance could lead to potential innovative drugs for MULIBREY nanism, including heart condition and carcinogenesis treatment.
Highlights
In 2001, Reymond et al used functional genomic techniques to show that the TRIpartite motif (TRIM), with the presence of a RING domain, B-box motifs, and a coiled-coil region, defines a family of 37 proteins with common cellular functions and compartmentalization
TRIM proteins are characterized by different subdomains, including a N-terminal domain containing the following: (i) a RING domain, a unique linear series of conserved cysteine and histidine residues of a zinc finger type that binds a pair of zinc atoms and is involved in mediating protein–protein interactions; (ii) one or two B-box motifs built of small peptide sequences containing finger-like protrusions involved in target protein recognition; and (iii) a coiled-coil region that mediates TRIM homo- or oligodimerization. (Figure 1) [2]
We focus on the role of TRIM37 in the normal cell and in pathological conditions, with an emphasis on the MULIBREY (MUscle-LIver-BRain-Eye).genetic disorder caused by TRIM37 mutations
Summary
In 2001, Reymond et al used functional genomic techniques to show that the TRIpartite motif (TRIM), with the presence of a RING domain, B-box motifs, and a coiled-coil region, defines a family of 37 proteins with common cellular functions and compartmentalization. Sardiello et al proposed to divide the TRIM family into two groups that differed in domain structure and genomic organization: Group 1 members are present in both vertebrates and invertebrates and possess a variety of C-terminal domains, and Group 2 members display a C-terminal SPRY domain and are absent in invertebrates (Figure 1) [4] Another classification based on domain organization has been proposed, with TRIM proteins being classified in subfamilies ranging from I to XI (C-I to C-XI) [2]. Nuclear localization signals (NLS) is a short sequence motif that is related to protein transport out of and into the nucleus
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