title: Tumor susceptibility gene 101 (TSG101) is a novel binding-partner for the class II Rab11-FIPs.
abstract: The Rab11-FIPs (Rab11-family interacting proteins; henceforth, FIPs) are a family of Rab11a/Rab11b/Rab25 GTPase effector proteins implicated in an assortment of intracellular trafficking processes. Through proteomic screening, we have identified TSG101 (tumor susceptibility gene 101), a component of the ESCRT-I (endosomal sorting complex required for transport) complex, as a novel FIP4-binding protein, which we find can also bind FIP3. We show that α-helical coiled-coil regions of both TSG101 and FIP4 mediate the interaction with the cognate protein, and that point mutations in the coiled-coil regions of both TSG101 and FIP4 abrogate the interaction. We find that expression of TSG101 and FIP4 mutants cause cytokinesis defects, but that the TSG101-FIP4 interaction is not required for localisation of TSG101 to the midbody/Flemming body during abscission. Together, these data suggest functional overlap between Rab11-controlled processes and components of the ESCRT pathway.
authors.affiliation: Molecular Cell Biology Laboratory, Department of Biochemistry, BioSciences Institute, University College Cork, Cork, Ireland.
authors.forename: Conor P
authors.initials: CP
authors.lastname: Horgan
authors.forename: Sara R
authors.initials: SR
authors.lastname: Hanscom
authors.forename: Eoin E
authors.initials: EE
authors.lastname: Kelly
authors.forename: Mary W
authors.initials: MW
authors.lastname: McCaffrey
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D048749:Cytokinesis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins; D000099177:Tsg101 Protein
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D051550:I-kappa B Kinase; D014157:Transcription Factors; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; D000099177:Tsg101 Protein; C491731:IKBKG protein, human