title: Essential role of hIST1 in cytokinesis.
abstract: The last steps of multivesicular body (MVB) formation, human immunodeficiency virus (HIV)-1 budding and cytokinesis require a functional endosomal sorting complex required for transport (ESCRT) machinery to facilitate topologically equivalent membrane fission events. Increased sodium tolerance (IST) 1, a new positive modulator of the ESCRT pathway, has been described recently, but an essential function of this highly conserved protein has not been identified. Here, we describe the previously uncharacterized KIAA0174 as the human homologue of IST1 (hIST1), and we report its conserved interaction with VPS4, CHMP1A/B, and LIP5. We also identify a microtubule interacting and transport (MIT) domain interacting motif (MIM) in hIST1 that is necessary for its interaction with VPS4, LIP5 and other MIT domain-containing proteins, namely, MITD1, AMSH, UBPY, and Spastin. Importantly, hIST1 is essential for cytokinesis in mammalian cells but not for HIV-1 budding, thus providing a novel mechanism of functional diversification of the ESCRT machinery. Last, we show that the hIST1 MIM activity is essential for cytokinesis, suggesting possible mechanisms to explain the role of hIST1 in the last step of mammalian cell division.
authors.affiliation: Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom.
authors.forename: Monica
authors.initials: M
authors.lastname: Agromayor
authors.forename: Jez G
authors.initials: JG
authors.lastname: Carlton
authors.forename: John P
authors.initials: JP
authors.lastname: Phelan
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Matthews
authors.forename: Leo M
authors.initials: LM
authors.lastname: Carlin
authors.forename: Simon
authors.initials: S
authors.lastname: Ameer-Beg
authors.forename: Katherine
authors.initials: K
authors.lastname: Bowers
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Serrano
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins
chemical_list: C443709:CHMP1A protein, human; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C533705:IST1 protein, human; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C499837:VTA1 protein, human; D033921:Vesicular Transport Proteins