title: Cyclin C interacts with steroid receptor coactivator 2 and upregulates cell cycle genes in MCF-7 cells.
abstract: Steroid receptor coactivator 2 (SRC-2) is a coactivator that regulates nuclear receptor activity. We previously reported that SRC-2 protein is degraded through the action of cAMP-dependent protein kinase A (PKA) and cAMP response element binding protein (CREB). In the study presented here, we aimed to identify proteins that interact with and thereby regulate SRC-2. We isolated cyclin C (CCNC) as an interacting partner with the SRC-2 degradation domain aa 347-758 in a yeast two-hybrid assay and confirmed direct interaction in an in vitro assay. The protein level of SRC-2 was increased with CCNC overexpression in COS-1 cells and decreased with CCNC silencing in COS-1 and MCF-7 cells. In a pulse-chase assay, we further show that silencing of CCNC resulted in a different SRC-2 degradation pattern during the first 6 h after the pulse. Finally, we provide evidence that CCNC regulates expression of cell cycle genes upregulated by SRC-2. In conclusion, our results suggest that CCNC temporarily protects SRC-2 against degradation and this event is involved in the transcriptional regulation of SRC-2 cell cycle target genes.
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen N-5021, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen N-5021, Norway. Electronic address: Olivera.Bozickovic@uib.no.
authors.forename: Olivera
authors.initials: O
authors.lastname: Bozickovic
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen N-5021, Norway. Electronic address: Tuyen.Hoang@uib.no.
authors.forename: Tuyen
authors.initials: T
authors.lastname: Hoang
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen N-5021, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen N-5021, Norway. Electronic address: fenneingvild@gmail.com.
authors.forename: Ingvild S
authors.initials: IS
authors.lastname: Fenne
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen N-5021, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen N-5021, Norway. Electronic address: Thomas.Helland@uib.no.
authors.forename: Thomas
authors.initials: T
authors.lastname: Helland
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen N-5021, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen N-5021, Norway. Electronic address: Linn.Skartveit@uib.no.
authors.forename: Linn
authors.initials: L
authors.lastname: Skartveit
authors.affiliation: Department of Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: ouchidam@md.okayama-u.ac.jp.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen N-5021, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen N-5021, Norway. Electronic address: Gunnar.Mellgren@uib.no.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen N-5021, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen N-5021, Norway. Electronic address: Jorn.Sagen@uib.no.
authors.forename: Jørn V
authors.initials: JV
authors.lastname: Sagen
mesh_terms: D000818:Animals; D019556:COS Cells; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D056745:Cyclin C / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D014158:Transcription, Genetic / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C503674:CCNC protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D056745:Cyclin C; D051958:Nuclear Receptor Coactivator 2; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: CycC; GRIP1; Mediator; NCoA2; TIF2