title: Phosphorylation-Dependent Activation of the ESCRT Function of ALIX in Cytokinetic Abscission and Retroviral Budding.
abstract: The modular adaptor protein ALIX is a key player in multiple ESCRT-III-mediated membrane remodeling processes. ALIX is normally present in a closed conformation due to an intramolecular interaction that renders ALIX unable to perform its ESCRT functions. Here we demonstrate that M phase-specific phosphorylation of the intramolecular interaction site within the proline-rich domain (PRD) of ALIX transforms cytosolic ALIX from closed to open conformation. Defining the role of this mechanism of ALIX regulation in three classical ESCRT-mediated processes revealed that phosphorylation of the intramolecular interaction site in the PRD is required for ALIX to function in cytokinetic abscission and retroviral budding, but not in multivesicular body sorting of activated epidermal growth factor receptor. Thus, phosphorylation of the intramolecular interaction site in the PRD is one of the major mechanisms that activates the ESCRT function of ALIX.
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA; Experimental Therapeutics Academic Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
authors: Sheng
authors: S
authors: Sun
authors: AbMax Biotechnology, Beijing 100085, China.
authors: Le
authors: L
authors: Sun
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
authors: Xi
authors: X
authors: Zhou
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
authors: Chuanfen
authors: C
authors: Wu
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
authors: Ruoning
authors: R
authors: Wang
authors: Experimental Therapeutics Academic Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Sue-Hwa
authors: SH
authors: Lin
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA; Experimental Therapeutics Academic Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: jkuang@mdanderson.org.
authors: Jian
authors: J
authors: Kuang
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D057146:Multivesicular Bodies / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C117020:PDCD6IP protein, human