title: JAB1/CSN5 inhibits the activity of Luman/CREB3 by promoting its degradation.
abstract: Luman/CREB3 (also called LZIP) is an endoplasmic reticulum (ER)-bound transcription factor that has been implicated in the ER stress response. In this study, we used the region of Luman containing the basic DNA-binding domain as bait in a yeast two-hybrid screen and identified the Jun activation domain-binding protein 1 (JAB1) or the COP9 signalosome complex unit 5 (CSN5) as an interacting protein. We confirmed their direct binding by glutathione S-transferase pull-down assays, and verified the existence of such interaction in the cellular environment by mammalian two-hybrid and co-immunoprecipitation assays. Deletion mapping studies revealed that the MPN domain in JAB1 was essential and sufficient for the binding. JAB1 also colocalized with Luman in transfected cells. More interestingly, the nuclear form of Luman was shown to promote the translocation of JAB1 into the nucleus. We found that overexpression of JAB1 shortened the half-life of Luman by 67%, and repressed its transactivation function on GAL4 and unfolded protein response element (UPRE)-containing promoters. We therefore propose that JAB1 is a novel binding partner of Luman, which negatively regulates the activity of Luman by promoting its degradation.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DenBoer
authors.forename: Aarti
authors.initials: A
authors.lastname: Iyer
authors.forename: Adam R R
authors.initials: AR
authors.lastname: McCluggage
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Martyn
authors.forename: Ray
authors.initials: R
authors.lastname: Lu
mesh_terms: D000818:Animals; D001483:Base Sequence; D000075686:COP9 Signalosome Complex; D019556:COS Cells; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017931:DNA Primers; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D010447:Peptide Hydrolases / Q000502:physiology*; D011485:Protein Binding; D059748:Proteolysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D014709:Vero Cells
chemical_list: C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex
keywords: ER; ER-associated degradation; ERAD; HSV; JAB1/CSN5; Luman/CREB3/LZIP; Protein degradation; Transcription factor; UPR; UPRE; Unfolded protein response; endoplasmic reticulum; herpes simplex virus; unfolded protein response