TRIM proteins in autophagy: selective sensors in cell damage and innate immune responses

Abstract

Autophagy, a main intracellular catabolic process, is induced in response to a variety of cellular stresses to promptly degrade harmful agents and to coordinate the activity of prosurvival and prodeath processes in order to determine the fate of the injured cells. While the main components of the autophagy machinery are well characterized, the molecular mechanisms that confer selectivity to this process both in terms of stress detection and cargo engulfment have only been partly elucidated. Here, we discuss the emerging role played by the E3 ubiquitin ligases of the TRIM family in regulating autophagy in physiological and pathological conditions, such as inflammation, infection, tumorigenesis, and muscle atrophy. TRIM proteins employ different strategies to regulate the activity of the core autophagy machinery, acting either as scaffold proteins or via ubiquitin-mediated mechanisms. Moreover, they confer high selectivity to the autophagy-mediated degradation as described for the innate immune response, where TRIM proteins mediate both the engulfment of pathogens within autophagosomes and modulate the immune response by controlling the stability of signaling regulators. Importantly, the elucidation of the molecular mechanisms underlying the regulation of autophagy by TRIMs is providing important insights into how selective types of autophagy are altered under pathological conditions, as recently shown in cancer and muscular dystrophy. Facts-TRIMs participate to the autophagic response to stress stimuli by regulating both autophagy induction and cargos recognition. -TRIMs modulate autophagy levels in ubiquitindependent and independent manners by interacting with either the autophagy core machinery or upstream signaling pathways. -TRIMs act as selective substrate receptors for the intracellular degradation of pathogens, immune signaling proteins, protein aggregates, and muscle proteins.

A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5α

“…VAMP8 and SNAP29). TRIM family proteins, including TRIM5, are increasingly recognized for modulating the actions and activities of these core autophagy factors [ 22 ].…”

A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5α

“…Finally, TRIM5 is one member of the large TRIM protein family. A very high percentage of the ~70 TRIMs in human genome act in regulating inflammatory signaling and antiviral defense and are increasingly linked to autophagy (29). Our findings presented here could potentially provide a groundwork for understanding the molecular underpinnings of these other TRIMs and how they coordinate their activities in autophagy and inflammation.…”

“…VAMP8 and SNAP29). TRIM family proteins, including TRIM5, are increasingly recognized for modulating the actions and activities of these core autophagy factors (29).…”

Development of a SNP linkage map and genome-wide association study for resistance to Aeromonas hydrophila in pacu (Piaractus mesopotamicus)

“…Tripartite motifcontaining protein 16 (trim16) gene is a part of tripartite motif family which has also been associated with QTL regions for A. hydrophila resistance in the hybrid cat sh [21]. Several studies have showed the involvement of this family of genes with signaling pathways for activation of murine macrophages [21], autophagic response [42], and interleukin secretion [43]. Interleukin 12 Receptor Subunit Beta2 (Il12rb2) is responsible in regulation of receptors to interleukin-12, a proin ammatory cytokine produced by phagocytic cells already identi ed in response to A. hydrophila infection [44].…”