title: Dual regulation of notch1 signaling pathway by adaptor protein fe65.
abstract: Notch1 receptor functions as a critical controller of cell fate decisions and also as a key regulator of cell growth, differentiation, and proliferation in invertebrates and vertebrates. In this study, we have demonstrated that the adaptor protein Fe65 attenuates Notch1 signaling via the accelerated degradation of the membrane-tethered Notch1 in the cytoplasm. Fe65 also suppresses Notch1 transcriptional activity via the dissociation of the Notch1-IC-recombining binding protein suppressor of hairless (RBP)-Jk complex within the nucleus. Fe65 is capable of forming a trimeric complex with Itch and membrane-tethered Notch1, and Fe65 enhances the protein degradation of membrane-tethered Notch1 via an Itch-dependent proteasomal pathway. Collectively, our results demonstrate that Fe65 carries out different functions depending on its location in the regulation of Notch1 signaling.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Jung-Soon
authors.initials: JS
authors.lastname: Mo
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Ann
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051881:Receptor, Notch1 / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C091042:APBB1 protein, human; C486243:Apbb1 protein, mouse; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497761:NOTCH1 protein, human; D009419:Nerve Tissue Proteins; C497762:Notch1 protein, mouse; D009687:Nuclear Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; C432966:ITCH protein, human; C471637:Itch protein, mouse; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex