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Kimura T
; Jain A
; Choi SW
; Mandell MA
; Johansen T
; Deretic V
Autophagy
2017[May]; 13
(5
): 989-990
PMID26983397
show ga
Selectivity of autophagy is achieved by target recognition; however, the number
of autophagy receptors identified so far is limited. In this study we demonstrate
that a subset of tripartite motif (TRIM) proteins mediate selective autophagy of
key regulators of inflammatory signaling. MEFV/TRIM20, and TRIM21 act as
autophagic receptors recognizing their cognate targets and delivering them for
autophagic degradation. MEFV recognizes the inflammasome components NLRP3, CASP1
and NLRP1, whereas TRIM21 specifically recognizes the activated, dimeric from of
IRF3 inducing type I interferon gene expression. MEFV and TRIM21 have a second
activity, whereby they act not only as receptors but also recruit and organize
key components of autophagic machinery consisting of ULK1, BECN1, ATG16L1, and
mammalian homologs of Atg8, with a preference for GABARAP. MEFV capacity to
organize the autophagy apparatus is affected by common mutations causing familial
Mediterranean fever. These findings reveal a general mode of action of TRIMs as
autophagic receptor-regulators performing a highly-selective type of autophagy
(precision autophagy), with MEFV specializing in the suppression of inflammasome
and CASP1 activation engendering IL1B/interleukin-1? production and implicated in
the form of cell death termed pyroptosis, whereas TRIM21 dampens type I
interferon responses.
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