2. Academic Validation
  3. TRIM50 regulates Beclin 1 proautophagic activity

TRIM50 regulates Beclin 1 proautophagic activity

  • Biochim Biophys Acta Mol Cell Res. 2018 Jun;1865(6):908-919. doi: 10.1016/j.bbamcr.2018.03.011.
Carmela Fusco 1,  Barbara Mandriani 1,  Martina Di Rienzo 2,  Lucia Micale 1,  Natascia Malerba 1,  Dario Cocciadiferro 3,  Eva Sjøttem 4,  Bartolomeo Augello 1,  Gabriella Maria Squeo 1,  Maria Teresa Pellico 1,  Ashish Jain 5,  Terje Johansen 4,  Gian Maria Fimia 6,  Giuseppe Merla 7
Affiliations

Affiliations

  • 1 Division of Medical Genetics, IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 71013 San Giovanni Rotondo, Italy.
  • 2 National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Rome, Italy; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • 3 Division of Medical Genetics, IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 71013 San Giovanni Rotondo, Italy; Ph.D Program in Experimental and Regenerative Medicine, University of Foggia, Italy.
  • 4 Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
  • 5 Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N-0379 Oslo, Norway.
  • 6 National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Rome, Italy; Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce 73100, Italy.
  • 7 Division of Medical Genetics, IRCCS Casa Sollievo Della Sofferenza, Viale Cappuccini, 71013 San Giovanni Rotondo, Italy. Electronic address: [email protected].
PMID: 29604308 DOI: 10.1016/j.bbamcr.2018.03.011
Abstract

Autophagy is a catabolic process needed for maintaining cell viability and homeostasis in response to numerous stress conditions. Emerging evidence indicates that the ubiquitin system has a major role in this process. TRIMs, an E3 ligase protein family, contribute to selective Autophagy acting as receptors and regulators of the Autophagy proteins recognizing endogenous or exogenous targets through intermediary autophagic tags, such as ubiquitin. Here we report that TRIM50 fosters the initiation phase of starvation-induced Autophagy and associates with Beclin1, a central component of Autophagy initiation complex. We show that TRIM50, via the RING domain, ubiquitinates Beclin 1 in a K63-dependent manner enhancing its binding with ULK1 and Autophagy activity. Finally, we found that the Lys-372 residue of TRIM50, critical for its own acetylation, is necessary for its E3 ligase activity that governs Beclin1 ubiquitination. Our study expands the roles of TRIMs in regulating selective Autophagy, revealing an acetylation-ubiquitination dependent control for Autophagy modulation.

Keywords

Autophagy; TRIM; Ubiquitination.

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