C/EBPδ targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression

• DOI: 10.1073/pnas.0913813107
• Publication Date: 2010-05-04T02:02:58Z
• Authors: Snehalata A. Pawar; Tapasree Roy Sarkar; Kuppusamy Balamur...; Shikha Sharan; Jun Wang; Youhong Zhang; Steven F. Dowdy; A-Mei Huang; Esta Sterneck
• Keywords: Cyclin B; Cyclin A; Cyclin D; Cyclin B1; F-box protein; Cyclin A2; Skp1; Cyclin E

The transcription factor CCAAT/enhancer binding protein δ (C/EBPδ, CEBPD, NFIL-6β) has tumor suppressor function; however, the molecular mechanism(s) by which C/EBPδ exerts its effect are largely unknown. Here, we report that induces expression of Cdc27 (APC3) subunit anaphase promoting complex/cyclosome (APC/C), results in polyubiquitination and degradation prooncogenic cell cycle regulator cyclin D1, also down-regulates B1, Skp2, Plk-1. In knockout mouse embryo fibroblasts (MEF) levels were reduced, whereas D1 increased even presence activated GSK-3β. Silencing C/EBPδ, Cdc27, or APC/C coactivator Cdh1 (FZR1) MCF-10A breast epithelial cells expression. Like contrast to was down-regulated several cancer lines, suggesting itself may be a suppressor. Cyclin is known substrate complex SKP1/CUL1/F-box (SCF), our studies show directs alternative APC/C. These findings shed light on role regulation APC/C, critical for most cellular processes.