SUMOylation of ZFP282 potentiates its positive effect on estrogen signaling in breast tumorigenesis

Abstract

Estrogen receptor α (ERα) plays critical roles in development and progression of breast cancer, and the coiled-coil co-activator (CoCoA) is an important ERα co-activator for estrogen-induced gene expression. The small ubiquitin-like modifier (SUMO) pathway is hyperactivated in breast cancer, but the mechanism by which SUMOylation regulates ERα-mediated transcription remains poorly understood. Here, we identified ZFP282 as a CoCoA binding protein. ZFP282 associates directly with ERα and cooperates synergistically with CoCoA to enhance ERα function. ZFP282 is required for estrogen-induced expression of ERα target genes and estrogen-dependent breast cancer cell growth and tumorigenesis. In addition, we found that ZFP282 is SUMOylated and that SUMOylation positively regulates the co-activator activity of ZFP282 by increasing its binding affinity to ERα and CoCoA and consequently increasing recruitment of ZFP282-CoCoA complex to the promoter of ERα target genes. These findings reveal essential roles for ZFP282 and its SUMOylation in estrogen signaling and breast tumorigenesis.

Positive regulation of β-catenin–PROX1 signaling axis by DBC1 in colon cancer progression

“…12,13,29,30 The immunoprecipitated DNAs were amplified by qPCR. The primers used are listed in Supplementary Information.…”

Coregulator Cell Cycle and Apoptosis Regulator 1 (CCAR1) Positively Regulates Adipocyte Differentiation through the Glucocorticoid Signaling Pathway

“…The cDNA was mixed with appropriate primers and LightCycler 480 SYBR Green I Master (Roche Applied Science), and the mixture was then analyzed with the LightCycler 480 System (Roche Applied Science). The primers used are listed in Table 1 or as follows: mC/EBP␣, mC/EBP␤, mC/EBP␦, and mGlut4 (4); h␤-actin (20); hGilz (12); hDUSP1 (22), hCARM1 (23), hCCAR1 (12), hCoCoA (16), hDBC1 (17), hTip60 (18), and hZNF282 (24). Results shown are mean and range of variation for duplicate PCR reactions from a single cDNA preparation and are representative of a minimum of two independent experiments.…”

A positive role of DBC1 in PEA3-mediated progression of estrogen receptor-negative breast cancer

“…33,35 The detailed method is provided in Supplementary Information. Animal experiments were conducted with the approval of the Institutional Animal Care and Use Committee of Laboratory Animal Research Center at Samsung Biomedical Research Institute.…”

“…11,[33][34][35] The immunoprecipitated DNAs were amplified by qPCR. The primers used are listed in Supplementary Information.…”