Cyclin C interacts with steroid receptor coactivator 2 and upregulates cell cycle genes in MCF-7 cells

Olivera Bozickovic, Tuyen Hoang, Ingvild S. Fenne, Thomas Helland, Linn Skartveit, Mamoru Ouchida, Gunnar Mellgren, Jørn V. Sagen

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)2383-2391
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number10
DOIs
Publication statusPublished - 2015

Keywords

  • CycC
  • GRIP1
  • Mediator
  • NCoA2
  • TIF2

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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