TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation

Michael A Mandell, Ashish Jain, Suresh Kumar, Moriah J Castleman, Tahira Anwar, Eeva-Liisa Eskelinen, Terje Johansen, Rytis Prerekis, Vojo Deretic

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

TRIM proteins contribute to selective autophagy, a process whereby cells target specific cargo for autophagic degradation. In a previously reported screen, TRIM17 acted as a prominent inhibitor of bulk autophagy, unlike the majority of TRIMs, which had positive roles. Nevertheless, TRIM17 showed biochemical hallmarks of autophagy-inducing TRIMs. To explain this paradox, here, we investigated how TRIM17 inhibits selective autophagic degradation of a subset of targets while promoting degradation of others. We traced the inhibitory function of TRIM17 to its actions on the anti-autophagy protein Mcl-1, which associates with and inactivates Beclin 1. TRIM17 expression stabilized Mcl-1–Beclin-1 complexes. Despite its ability to inhibit certain types of selective autophagy, TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. The selective loss of anti-autophagy Mcl-1 from TRIM17–Beclin-1 complexes at midbodies correlated with the ability of TRIM17 to promote midbody removal. This study further expands the roles of TRIMs in regulating selective autophagy by showing that a single TRIM can, depending upon a target, either positively or negatively regulate autophagy.
Alkuperäiskielienglanti
LehtiJournal of Cell Science
Vuosikerta129
Sivut3562-3573
ISSN0021-9533
DOI - pysyväislinkit
TilaJulkaistu - 1 lokakuuta 2016
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 1182 Biokemia, solu- ja molekyylibiologia

Lainaa tätä

Mandell, Michael A ; Jain, Ashish ; Kumar, Suresh ; Castleman, Moriah J ; Anwar, Tahira ; Eskelinen, Eeva-Liisa ; Johansen, Terje ; Prerekis, Rytis ; Deretic, Vojo. / TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation. Julkaisussa: Journal of Cell Science. 2016 ; Vuosikerta 129. Sivut 3562-3573.
@article{37400bee4260422d8aa364dca84c82ff,
title = "TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation",
abstract = "TRIM proteins contribute to selective autophagy, a process whereby cells target specific cargo for autophagic degradation. In a previously reported screen, TRIM17 acted as a prominent inhibitor of bulk autophagy, unlike the majority of TRIMs, which had positive roles. Nevertheless, TRIM17 showed biochemical hallmarks of autophagy-inducing TRIMs. To explain this paradox, here, we investigated how TRIM17 inhibits selective autophagic degradation of a subset of targets while promoting degradation of others. We traced the inhibitory function of TRIM17 to its actions on the anti-autophagy protein Mcl-1, which associates with and inactivates Beclin 1. TRIM17 expression stabilized Mcl-1–Beclin-1 complexes. Despite its ability to inhibit certain types of selective autophagy, TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. The selective loss of anti-autophagy Mcl-1 from TRIM17–Beclin-1 complexes at midbodies correlated with the ability of TRIM17 to promote midbody removal. This study further expands the roles of TRIMs in regulating selective autophagy by showing that a single TRIM can, depending upon a target, either positively or negatively regulate autophagy.",
keywords = "1182 Biochemistry, cell and molecular biology, HIV, Mcl-1, midbody, selective autophagy, tripartite motif",
author = "Mandell, {Michael A} and Ashish Jain and Suresh Kumar and Castleman, {Moriah J} and Tahira Anwar and Eeva-Liisa Eskelinen and Terje Johansen and Rytis Prerekis and Vojo Deretic",
year = "2016",
month = "10",
day = "1",
doi = "10.1242/jcs.190017",
language = "English",
volume = "129",
pages = "3562--3573",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",

}

Mandell, MA, Jain, A, Kumar, S, Castleman, MJ, Anwar, T, Eskelinen, E-L, Johansen, T, Prerekis, R & Deretic, V 2016, 'TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation' Journal of Cell Science, Vuosikerta 129, Sivut 3562-3573. https://doi.org/10.1242/jcs.190017

TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation. / Mandell, Michael A; Jain, Ashish; Kumar, Suresh; Castleman, Moriah J; Anwar, Tahira; Eskelinen, Eeva-Liisa; Johansen, Terje; Prerekis, Rytis; Deretic, Vojo.

julkaisussa: Journal of Cell Science, Vuosikerta 129, 01.10.2016, s. 3562-3573.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation

AU - Mandell, Michael A

AU - Jain, Ashish

AU - Kumar, Suresh

AU - Castleman, Moriah J

AU - Anwar, Tahira

AU - Eskelinen, Eeva-Liisa

AU - Johansen, Terje

AU - Prerekis, Rytis

AU - Deretic, Vojo

PY - 2016/10/1

Y1 - 2016/10/1

N2 - TRIM proteins contribute to selective autophagy, a process whereby cells target specific cargo for autophagic degradation. In a previously reported screen, TRIM17 acted as a prominent inhibitor of bulk autophagy, unlike the majority of TRIMs, which had positive roles. Nevertheless, TRIM17 showed biochemical hallmarks of autophagy-inducing TRIMs. To explain this paradox, here, we investigated how TRIM17 inhibits selective autophagic degradation of a subset of targets while promoting degradation of others. We traced the inhibitory function of TRIM17 to its actions on the anti-autophagy protein Mcl-1, which associates with and inactivates Beclin 1. TRIM17 expression stabilized Mcl-1–Beclin-1 complexes. Despite its ability to inhibit certain types of selective autophagy, TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. The selective loss of anti-autophagy Mcl-1 from TRIM17–Beclin-1 complexes at midbodies correlated with the ability of TRIM17 to promote midbody removal. This study further expands the roles of TRIMs in regulating selective autophagy by showing that a single TRIM can, depending upon a target, either positively or negatively regulate autophagy.

AB - TRIM proteins contribute to selective autophagy, a process whereby cells target specific cargo for autophagic degradation. In a previously reported screen, TRIM17 acted as a prominent inhibitor of bulk autophagy, unlike the majority of TRIMs, which had positive roles. Nevertheless, TRIM17 showed biochemical hallmarks of autophagy-inducing TRIMs. To explain this paradox, here, we investigated how TRIM17 inhibits selective autophagic degradation of a subset of targets while promoting degradation of others. We traced the inhibitory function of TRIM17 to its actions on the anti-autophagy protein Mcl-1, which associates with and inactivates Beclin 1. TRIM17 expression stabilized Mcl-1–Beclin-1 complexes. Despite its ability to inhibit certain types of selective autophagy, TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. The selective loss of anti-autophagy Mcl-1 from TRIM17–Beclin-1 complexes at midbodies correlated with the ability of TRIM17 to promote midbody removal. This study further expands the roles of TRIMs in regulating selective autophagy by showing that a single TRIM can, depending upon a target, either positively or negatively regulate autophagy.

KW - 1182 Biochemistry, cell and molecular biology

KW - HIV

KW - Mcl-1

KW - midbody

KW - selective autophagy

KW - tripartite motif

U2 - 10.1242/jcs.190017

DO - 10.1242/jcs.190017

M3 - Article

VL - 129

SP - 3562

EP - 3573

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

ER -