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ERR? splice variants differentially regulate cell cycle progression.

ABSTRACT: 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? (ERR?sf) and ERR?2, and identify their differing roles in cell cycle regulation. Using DY131 (a synthetic agonist of ERR?), splice-variant selective shRNA, and exogenous ERR?sf and ERR?2 cDNAs, we demonstrate the role of ERR?sf in mediating the G1 checkpoint through p21. We also show ERR?sf is required for DY131-induced cellular senescence. A key novel finding of this study is that ERR?2 can mediate a G2/M arrest in response to DY131. In the absence of ERR?2, 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.

SUBMITTER: Heckler MM

PROVIDER: S-EPMC4614362 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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ERRβ splice variants differentially regulate cell cycle progression.

Heckler Mary Mazzotta MM Riggins Rebecca B RB

Cell cycle (Georgetown, Tex.) 20150101 1

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 ERRβ splice variants, short form ERRβ (ERRβsf) and ERRβ2, and identify their differing roles in cell cycle regulation. Using DY131 (a synthetic agonist of ERRβ), splice-variant selective shRNA, and exogenou ...[more]

PMID: 25496115

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