title: SUMOylation of ZFP282 potentiates its positive effect on estrogen signaling in breast tumorigenesis.
abstract: Estrogen receptor α (ERα) has critical roles in the 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.
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: E J
authors.initials: EJ
authors.lastname: Yu
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: M J
authors.initials: MJ
authors.lastname: Kim
authors.forename: W-Y
authors.initials: WY
authors.lastname: Seo
authors.forename: K-A
authors.initials: KA
authors.lastname: Song
authors.forename: M-S
authors.initials: MS
authors.lastname: Kang
authors.forename: C K
authors.initials: CK
authors.lastname: Yang
authors.forename: M R
authors.initials: MR
authors.lastname: Stallcup
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D058207:Sumoylation; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha