TRIM proteins regulate autophagy: TRIM5 is a selective autophagy receptor mediating HIV-1 restriction - PubMed (original) (raw)

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TRIM proteins regulate autophagy: TRIM5 is a selective autophagy receptor mediating HIV-1 restriction

Michael A Mandell et al. Autophagy. 2014.

Abstract

The tripartite motif protein family (TRIM) constitutes a class of immune-regulated proteins with antiviral, immune, cancer, and other properties reminiscent of those ascribed to autophagy. We show that TRIMs have dual roles in autophagy: as regulators and as cargo receptors. As regulators, TRIMs nucleate the core autophagy machinery by acting as platforms that assemble ULK1 and BECN1 into a functional complex in preparation for autophagy. TRIMs also act as novel selective autophagy receptors as exemplified by TRIM5/TRIM5α, a known HIV-1 restriction factor with a hitherto poorly defined mode of action. TRIM5 recognizes and targets HIV-1 for autophagic destruction. TRIM5 interactions with mammalian Atg8 proteins are required for this effector function. This establishes TRIM family members as regulators of autophagy, explains the antiretroviral mechanism of TRIM5, and defines a new basis for selective autophagy.

Keywords: HIV-1 restriction; TRIM5; selective autophagy.

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Figure 1.

Figure 1.

Top, TRIM5 promotes autophagy by acting as a platform for the assembly of active ULK1 and BECN1 complexes and rhesus (but not human) TRIM5 delivers incoming HIV-1 capsids for autophagic degradation by directly binding both the viral capsid and mammalian Atg8s. Assembly of ULK1, BECN1, and mammalian Atg8s is a conserved feature in most TRIMs. We propose that TRIMs use their SPRY or other cargo recognition domains for the autophagic targeting of a wide variety of microbial and endogenous cellular substrates. Shown is a generic TRIM domain organization; the table lists TRIMs that affect autophagy in our siRNA screen.

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