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.
authors: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Albuquerque, NE NM 87131 USA mmandell@salud.unm.edu vderetic@salud.unm.edu.
authors: Michael A
authors: 0000-0002-5773-2806
authors: MA
authors: Mandell
authors: Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø 9037, Norway Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo N-0379, Norway Center for Cancer Biomedicine, Faculty of Medicine, University of Oslow, Montebello, Oslo N-0379, Norway.
authors: Ashish
authors: A
authors: Jain
authors: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Albuquerque, NE NM 87131 USA.
authors: Suresh
authors: S
authors: Kumar
authors: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Albuquerque, NE NM 87131 USA.
authors: Moriah J
authors: MJ
authors: Castleman
authors: Department of Biosciences, University of Helsinki, Helsinki 00014, Finland.
authors: Tahira
authors: T
authors: Anwar
authors: Department of Biosciences, University of Helsinki, Helsinki 00014, Finland.
authors: Eeva-Liisa
authors: EL
authors: Eskelinen
authors: Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo N-0379, Norway.
authors: Terje
authors: T
authors: Johansen
authors: Department of Cell and Developmental Biology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA.
authors: Rytis
authors: R
authors: Prekeris
authors: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Albuquerque, NE NM 87131 USA mmandell@salud.unm.edu vderetic@salud.unm.edu.
authors: Vojo
authors: V
authors: Deretic
mesh_terms: D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism; D002213:Capsid / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D034741:RNA, Small Interfering; D000070584:Tripartite Motif Proteins; C000597019:tripartite motif-containing protein 15, human; C115437:TRIM17 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: HIV; Mcl-1; Midbody; Selective autophagy; Tripartite-motif