title: In human monocyte derived dendritic cells SOCS1 interacting with CYTIP induces the degradation of CYTIP by the proteasome.
abstract: CYTIP (cytohesin interacting protein) is an intracellular molecule induced in dendritic cells during maturation. CYTIP modulates the binding intensity of the adhesion molecule LFA-1. If dendritic cells are silenced for CYTIP they keep longer contacts with T-cells resulting in a lower T cell stimulation. We identified Suppressor of cytokine signaling-1 (SOCS-1) as a binding partner for CYTIP in human monocyte derived dendritic cells. In Western blot analyses we found that CYTIP expression is down regulated at later time points, starting at about 72 hours after induction of maturation. To investigate a possible role for SOCS-1 in taking CYTIP to the degradation machinery of the cell we measured endogenous CYTIP protein levels in mature dendritic cells transfected with SOCS-1 encoding plasmid in quantitative Western blot analyses. We observed lower amounts of endogenous CYTIP in mature dendritic cells transfected with SOCS-1 encoding plasmid compared with untransfected dendritic cells. Experiments with the proteasome-inhibitor Bortezomib/Velcade® show stable CYTIP expression levels in dendritic cells. In addition, we show that CYTIP in dendritic cells matured for 48 hours is ubiquitinated and thus ready for degradation. We here describe a newly identified binding partner of CYTIP, SOCS-1, and confirm its function in regulating the degradation of CYTIP by the proteasome.
authors.affiliation: Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Grabher
authors.forename: Susanne
authors.initials: S
authors.lastname: Hofer
authors.forename: Daniela
authors.initials: D
authors.lastname: Ortner
authors.forename: Christine
authors.initials: C
authors.lastname: Heufler
mesh_terms: D015153:Blotting, Western; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D059748:Proteolysis; D011719:Pyrazines / Q000494:pharmacology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: D001897:Boronic Acids; C084539:CYTIP protein, human; D011719:Pyrazines; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex