title: The upstream stimulatory factor USF1 is regulated by protein kinase CK2 phosphorylation.
abstract: The upstream stimulatory factors 1 (USF1) and 2 (USF2) are transcription factors which bind to E-box motifs of various promoters regulating a variety of different cellular processes. Only little is known about the regulation of USFs. Here, we identified protein kinase CK2 as an enzyme that phosphorylates USF1 but not USF2. Using deletion mutants and point mutants we were able to identify threonine 100 as the major phosphorylation site for CK2. It is well known that USF1 and USF2 form hetero-dimers. Binding studies revealed that the inhibition of CK2 kinase activity by a specific inhibitor enhanced binding of USF1 to USF2. Furthermore, transactivation studies showed that the inhibition of CK2 phosphorylation of USF1 stimulated transcription from the glucokinase promoter as well as the fatty acid synthetase promoter but not from the heme oxygenase-1 promoter. Thus, we have shown for the first time that CK2 phosphorylation of USF1 modulates two functionally important properties of USF1, namely hetero-dimerization and transactivation.
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lupp
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany. Electronic address: claudia.goetz@uks.eu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Götz
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
authors.forename: Sunia
authors.initials: S
authors.lastname: Khadouma
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Tina
authors.initials: T
authors.lastname: Horbach
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Elitsa Y
authors.initials: EY
authors.lastname: Dimova
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Bohrer
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kietzmann
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Montenarh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism*; D020035:Holoenzymes / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects; D051381:Rats; D013379:Substrate Specificity / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D051720:Upstream Stimulatory Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020035:Holoenzymes; D047428:Protein Kinase Inhibitors; C497181:USF1 protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D010769:Phosphothreonine; D047390:Casein Kinase II
keywords: Hetero-dimerization; Phosphorylation; Protein kinase CK2; Transactivation; Transcription factor