TRIM50 regulates Beclin 1 proautophagic activity

Carmela Fusco, Barbara Mandriani, Martina Di Rienzo, Lucia Micale, Natascia Malerba, Dario Cocciadiferro, Eva Sjøttem, Bartolomeo Augello, Gabriella Maria Squeo, Maria Teresa Pellico, Ashish Jain, Terje Johansen, Gian Maria Fimia, Giuseppe Merla

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)908-919
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number6
Publication statusPublished - Jun 1 2018


  • Autophagy
  • TRIM
  • Ubiquitination

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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