TRIM/RBCC, a novel class of ‘single protein RING finger’ E3 ubiquitin ligases

Abstract

The TRIM/RBCC proteins are defined by the presence of the tripartite motif composed of a RING domain, one or two B-box motifs and a coiled-coil region. These proteins are involved in a plethora of cellular processes such as apoptosis, cell cycle regulation and viral response. Consistently, their alteration results in many diverse pathological conditions. The highly conserved modular structure of these proteins suggests that a common biochemical function may underlie their assorted cellular roles. Here, we review recent data indicating that some TRIM/RBCC proteins are implicated in ubiquitination and propose that this large protein family represents a novel class of 'single protein RING finger' ubiquitin E3 ligases.

Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity

“…Tripartite motif (TRIM) E3 ligases constitute one of the largest subfamilies of RING E3s and regulate many cellular processes with a large proportion of TRIM family members being important in the regulation of innate immune responses (Meroni & Diez‐Roux, 2005; Hatakeyama, 2011; Napolitano & Meroni, 2012; Rajsbaum et al , 2014). TRIM ligases share a conserved domain architecture that consists of an N‐terminally located TRIM motif and a C‐terminal region of variable composition that often contains protein interaction domains and may act as a substrate‐recognition module.…”

Generation of human TRIM5α mutants with high HIV-1 restriction activity

“…1,2 TRIM5a was isolated in 2004 as the factor governing the resistance of rhesus macaque monkeys to transduction by human immunodeficiency virus (HIV)-1 vectors. 3 Shortly thereafter, most primates were shown to encode TRIM5a orthologues each having the capacity to restrict a particular range of retroviruses.…”

Trim11 increases expression of dopamine β-hydroxylase gene by interacting with Phox2b

“…Trim11 belongs to the TRIM family of proteins also known as RBCC proteins. These proteins contain a RING domain, one or two zinc-binding motifs called B-boxes, a coiled-coil domain, and the B30.2 or SPRY domain [24][25][26]. The RING domain contains a specialized zinc finger that binds two zinc atoms and has ubiquitin E3 ligase activity.…”

“…Though its function is not clearly attributed, proteinprotein interaction activity has been suggested for B30.2 domain [27]. Members of the TRIM family are implicated in various cellular processes, such as cell proliferation, differentiation, oncogenesis, apoptosis, viral response, and development [24,25]. Recent bioinformatics approaches have been identified new TRIM proteins [16,25] -68 genes and one pseudogene have been identified in human.…”