title: Ambra1 at a glance.
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 correlate with 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 pro-autophagic protein in cellular pathophysiology.
authors.affiliation: Unit of Cell stress and survival, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark IRCCS Fondazione, Santa Lucia, 00143 Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cianfanelli
authors.affiliation: Unit of Cell stress and survival, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: De Zio
authors.affiliation: IRCCS Fondazione, Santa Lucia, 00143 Rome, Italy Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Di Bartolomeo
authors.affiliation: IRCCS Fondazione, Santa Lucia, 00143 Rome, Italy Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nazio
authors.affiliation: IRCCS Fondazione, Santa Lucia, 00143 Rome, Italy Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Flavie
authors.initials: F
authors.lastname: Strappazzon
authors.affiliation: Unit of Cell stress and survival, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark IRCCS Fondazione, Santa Lucia, 00143 Rome, Italy Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy cecconi@cancer.dk.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins
keywords: Autophagy; Cancer biology; Cell cycle; Mitochondria; Nervous system