title: C/EBP family transcription factors are degraded by the proteasome but stabilized by forming dimer.
abstract: CCAAT/enhancer-binding protein (C/EBP) family transcription factors are critical for transcription of several genes involved in tissue development and cellular function, proliferation, and differentiation. Here we show that inhibitory/regulatory C/EBP family proteins, Ig/EBP (C/EBPgamma) and CHOP (C/EBPzeta), but not positively functioning NF-IL6 (C/EBPbeta), are constitutively multiubiquitinated and subsequently degraded by the proteasome. In addition, ubiquitination and degradation of these proteins are suppressed by forming dimer through their leucine zipper domains. Deletion of leucine zipper domain in NF-IL6 caused the loss of its homodimerization activity and the degradation of protein by the ubiquitin-proteasome system. In addition, Ig/EBP with its leucine zipper domain substituted for that of NF-IL6 formed homodimer and was stabilized. These observations suggest that mammalian cells equip a novel regulatory system abrogating the excess C/EBP family transcription factors bereft of dimerizing partner.
authors.affiliation: Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Mizuho, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hattori
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Ohoka
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Onozaki
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002460:Cell Line / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology; D007976:Leupeptins / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C405462:CCAAT-enhancer-binding protein-gamma; C497249:DDIT3 protein, human; D007976:Leupeptins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D011500:Protein Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D051742:Transcription Factor CHOP; D003513:Cycloheximide; D008741:Methyl Methanesulfonate; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde