title: SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.
abstract: LITAF is a small cellular protein with an unknown function. The C-terminus of LITAF contains a highly conserved domain termed the SIMPLE-like domain (SLD), while the N-terminus contains two PPXY motifs that mediate protein-protein interactions with WW-domain containing proteins. LITAF also harbors two endosome/lysosome targeting sequences at its C-terminus, but there has been conflicting reports regarding its intracellular localization. Here, we demonstrate that LITAF is localized to the late endosome/lysosomal compartment in a variety of cell lines. We also show that Itch, a WW-domain containing protein, and LITAF strongly interact and that this interaction depends on the two PPXY motifs in the N-terminus of LITAF. Interestingly, co-expression of LITAF with Itch induces major changes in Itch intracellular localization, bringing Itch from the trans-Golgi network to lysosomes. We show that this re-localization is dependent upon the interaction with the PPXY sequences of LITAF, since disruption of these binding motifs completely abrogates Itch re-localization.
authors.affiliation: Department of Biology, Trent University, Peterborough, Canada.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Eaton
authors.forename: Guillaume
authors.initials: G
authors.lastname: Desrochers
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Drory
authors.forename: Julie
authors.initials: J
authors.lastname: Metcalf
authors.forename: Annie
authors.initials: A
authors.lastname: Angers
authors.forename: Craig R
authors.initials: CR
authors.lastname: Brunetti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002451:Cell Compartmentation; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C118738:LITAF protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases