To Ubiquitinate or Not to Ubiquitinate: TRIM17 in Cell Life and Death

Abstract

TRIM17 is a member of the TRIM family, a large class of RING-containing E3 ubiquitin-ligases. It is expressed at low levels in adult tissues, except in testis and in some brain regions. However, it can be highly induced in stress conditions which makes it a putative stress sensor required for the triggering of key cellular responses. As most TRIM members, TRIM17 can act as an E3 ubiquitin-ligase and promote the degradation by the proteasome of substrates such as the antiapoptotic protein MCL1. Intriguingly, TRIM17 can also prevent the ubiquitination of other proteins and stabilize them, by binding to other TRIM proteins and inhibiting their E3 ubiquitin-ligase activity. This duality of action confers several pivotal roles to TRIM17 in crucial cellular processes such as apoptosis, autophagy or cell division, but also in pathological conditions as diverse as Parkinson's disease or cancer. Here, in addition to recent data that endorse this duality, we review what is currently known from public databases and the literature about TRIM17 gene regulation and expression, TRIM17 protein structure and interactions, as well as its involvement in cell physiology and human disorders.

Keywords: Parkinson’s disease; TRIM17; apoptosis; autism; autophagy; cancer; mitosis; proteolysis; ubiquitination.

Figure 1

Classification of the TRIM proteins family. In bold, TRIM17 and its known TRIM partners described in this review. Adapted from [19,20].

Figure 2

(a) Screenshot from NCBI’s Genome Data Viewer. The data track MANE Project (release v0.93) shows TRIM17 and TRIM11 genes’ localization and transcripts (NCBI’s Refseq names NM_016102.4 and NM_145214.3, respectively) on GRCh38.p13 primary assembly; (b) gene model (ENSG00000162931.11) and TRIM17 mRNA isoforms (from gtexportal.org, 21 February 2021, Source: HGNC Symbol; Acc: HGNC:13430).

Figure 3

Cell type expression profile of human TRIM17 gene (from https://gtexportal.org/home/, 21 February 2021). Data source: GTEx Analysis Release V8 (dbGaP Accession phs000424.v8.p2); TPM: transcripts per million (for additional information, see https://academic.oup.com/bioinformatics/article/26/4/493/243395).

Figure 4

Species conservation of TRIM17 RING (a), Bbox2 (b), coiled-coil (c) and PRY-SPRY (d) domain sequences and comparison with other TRIMs and known consensus sequences. In bold, TRIM17 conserved residues in consensus sequence or shared by other TRIMs. In red, conserved residues through species. In green, residues highly conserved through species possibly involved in specificity of TRIM17.

Figure 5

(a) Schematic representation of the expected domain architecture of TRIM17 isoforms and the corresponding protein coding lengths (in amino acids) (from ensembl.org, 21 February 2021); (b) expression profile of TRIM17 isoforms [Source:HGNC Symbol;Acc:HGNC:13430].

Figure 6

(a) Predicted monomeric 3D structure of tripartite motif and PRY-SPRY domains of human TRIM17 (Q9Y577) based on TRIM28 (6QAJ.1A) and PYRIN (2WL1.1A), respectively (from Swiss Model Repository database); (b) predicted 3D structure of TRIM17 homodimers based on homodimers of tripartite and PRY-SPRY domains of TRIM28 and PYRIN respectively (from Swiss Model Repository database).

Figure 7

TRIM and E2 partners of TRIM17 from experimental data.

Figure 8

Cellular functions of TRIM17.