ERR beta splice variants differentially regulate cell cycle progression

作者：Heckler Mary Mazzotta^*; Riggins Rebecca B

来源：Cell Cycle, 2015, 14(1): 31-45.

DOI：10.4161/15384101.2014.972886

• alternative splicing
• ESRRB
• ERRbeta
• nuclear receptor
• p53
• senescence
• cell cycle

Orphan receptors comprise nearly half of all members of the nuclear receptor superfamily. Despite having broad structural similarities to the classical estrogen receptors, estrogen-related receptors (ERRs) have their own unique DNA response elements and functions. In this study, we focus on 2 ERR splice variants, short form ERR (ERRsf) and ERR2, and identify their differing roles in cell cycle regulation. Using DY131 (a synthetic agonist of ERR), splice-variant selective shRNA, and exogenous ERRsf and ERR2 cDNAs, we demonstrate the role of ERRsf in mediating the G1 checkpoint through p21. We also show ERRsf is required for DY131-induced cellular senescence. A key novel finding of this study is that ERR2 can mediate a G2/M arrest in response to DY131. In the absence of ERR2, the DY131-induced G2/M arrest is reversed, and this is accompanied by p21 induction and a G1 arrest. This study illustrates novel functions for ERR splice variants and provides evidence for splice variant interaction.

• 出版日期2015-1-1