High-throughput cell-based screening reveals a role for ZNF131 as a repressor of ERalpha signaling

Abstract

Background: Estrogen receptor α (ERα) is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ERα, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE) with a reporter gene. This allowed the cellular activity of ERα, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2.

UHRF2, a Ubiquitin E3 Ligase, Acts as a Small Ubiquitin-like Modifier E3 Ligase for Zinc Finger Protein 131

“…Previous reports, including ours, demonstrated that ZNF13 acts as a repressor of estrogen receptor ␣-mediated trans-activation (30,42,43). In addition, we previously reported that the SUMOylation of ZNF131 negatively regulates estrogen receptor ␣-mediated signaling and estrogen-induced cell proliferation in breast cancer cells (30).…”

FBI-1 functions as a novel AR co-repressor in prostate cancer cells

“…However, whether FBI-1 could regulate the signaling of nuclear receptors such as AR and ER was still unclear [9,11,12,21]. Recently, zinc finger protein 131 (ZN131), a typical member of the BTB/ POZ family, was found to function as a repressor of estrogen receptor alpha (ERa) and repress ligand-dependent ERa transactivitation and the expression of pS2, an ERa target gene [22]. PLZF, the homolog of FBI-1, is an androgen-responsive gene and can inhibit LNCaP proliferation.…”

Small Ubiquitin-like Modifier (SUMO) Modification of Zinc Finger Protein 131 Potentiates Its Negative Effect on Estrogen Signaling

“…on Estrogen Signaling-Next, we examined whether ZNF131 negatively regulates estrogen signaling, based on a previous report that ZNF131 inhibits ligand-dependent trans-activation by ER␣ (10). ER␣-positive MCF-7 breast cancer cells were transfected with a luciferase reporter plasmid containing four tandem EREs in the presence or absence of HA-ZNF131.…”

“…Whereas ZNF131 was previously reported to suppress ER␣ target gene expression (10), its molecular and regulatory mechanism has not yet been characterized. Here, we identify ZNF131 as a target for SUMOylation and report that hPc2 is its SUMO E3 ligase.…”

“…Zinc finger protein 131 (ZNF131) is a member of the POZ zinc finger (POZ-ZF) protein superfamily and was initially linked with developmental disorders (9). Using a high-throughput, cell-based, and functional screening platform created by linking the ERE with a reporter gene, ZNF131 has been shown to suppress ER␣ target gene expression (10).…”