Ambra1 at a glance

Valentina Cianfanelli, Daniela De Zio, Sabrina Di Bartolomeo, Francesca Nazio, Flavie Strappazzon, Francesco Cecconi

Research output: Contribution to journalArticlepeer-review

Abstract

The activating molecule in Beclin-1-regulated autophagy (Ambra1), also known as autophagy/Beclin-1 regulator 1, is a highly intrinsically disordered and vertebrate-conserved adapter protein that is part of the autophagy signaling network. It acts in an early step of mammalian target of rapamycin complex 1 (mTORC1)-dependent autophagy by favouring formation of the autophagosome core complex. However, recent studies have revealed that Ambra1 can also coordinate a cell response upon starvation or other stresses that involve translocation of the autophagosome core complex to the endoplasmic reticulum (ER), regulative ubiquitylation and stabilization of the kinase ULK1, selective mitochondria removal and cell cycle downregulation. Moreover, Ambra1 itself appears to be targeted by a number of regulatory processes, such as cullin-dependent degradation, caspase cleavage and several modifications, ranging from phosphorylation to ubiquitylation. Altogether, this complex network of regulation highlights the importance of Ambra1 in crucial physiological events, including metabolism, cell death and cell division. In addition, Ambra1 is an important regulator of embryonic development, and its mutation or inactivation has been shown to correlatewith several pathologies of the nervous system and to be involved in carcinogenesis. In this Cell Science at a Glance article and the accompanying poster, we discuss recent advances in the Ambra1 field, particularly the role of this proautophagic protein in cellular pathophysiology.

Original languageEnglish
Pages (from-to)2003-2008
Number of pages6
JournalJournal of Cell Science
Volume128
Issue number11
DOIs
Publication statusPublished - 2015

Keywords

  • Autophagy
  • Cancer biology
  • Cell cycle
  • Mitochondria
  • Nervous system

ASJC Scopus subject areas

  • Cell Biology

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