FHL2, UBC9, and PIAS1 are novel estrogen receptor α-interacting proteins

Sakiko Kobayashi, Hirotaka Shibata, Kenichi Yokota, Noriko Suda, Ayano Takeda, Isao Kurihara, Ikuo Saito, Takao Saruta

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Estrogen plays important roles in the pathophysiology of atherosclerosis and cardiovascular diseases mediated by estrogen receptor α (ERα). To elucidate the molecular mechanisms, we screened ERα-interacting proteins from a human heart cDNA library using a yeast two-hybrid system, and identified the four and a half of LIM-only protein 2 (FHL2). FHL2 interacted with ERα in the presence of 17β-estradiol, but not of tamoxifen or raloxifene in yeast. FHL2 mainly interacted with N-terminal A/B domain of ERα but not C-terminal ligand-binding domain. However, overexpression of full-length FHL2 did not affect ERα-dependent transcriptional activities of a reporter containing 3 copies of estrogen response element in COS-1 cells. Since tissue distribution of FHL2 was highly restricted to the heart, the function of FHL2 may be observed in a cell type- or promoter-specific manner. We have also detected strong interactions of ERα with Ubc9 and PIAS1 in yeast. Ubc9 and PIAS1, small ubiquitin-related modifier-1 (SUMO-1) conjugating enzyme and ligase, respectively, markedly interacted with ERα in a 17β-estradiol-dependent manner. These proteins mainly interacted with the DNA-binding and ligand-binding domains of ERα. Overexpression of Ubc9 or PIAS1 potentiated ERα-mediated transcriptional activities in COS-1 cells in a dose-dependent manner, indicating that both Ubc9 and PIAS1 function as coactivators of ERα. In addition, the SUMOylation-defective mutant, Ubc9 (C93S) continued to enhance ERα-dependent transcriptional activities. These findings suggest that coactivator abilities and SUMOylation capacities of Ubc9 and PIAS1 are separable and distinct. The present studies indicate that ERα exhibit tissue-specific functions utilizing multiple tissue-restricted receptor-interacting proteins.

Original languageEnglish
Pages (from-to)617-621
Number of pages5
JournalEndocrine Research
Volume30
Issue number4
DOIs
Publication statusPublished - 2004

Fingerprint

Receptor-Interacting Protein Serine-Threonine Kinases
Estrogen Receptors
Sumoylation
COS Cells
Estradiol
Estrogens
estrophilin
Yeasts
Ligands
Two-Hybrid System Techniques
Response Elements
Tissue Distribution
Tamoxifen
Ligases
Ubiquitin
Gene Library
Atherosclerosis
Proteins
Cardiovascular Diseases

Keywords

  • Coactivator
  • ERα
  • FHL2
  • PIAS1
  • Ubc9

ASJC Scopus subject areas

  • Endocrinology

Cite this

FHL2, UBC9, and PIAS1 are novel estrogen receptor α-interacting proteins. / Kobayashi, Sakiko; Shibata, Hirotaka; Yokota, Kenichi; Suda, Noriko; Takeda, Ayano; Kurihara, Isao; Saito, Ikuo; Saruta, Takao.

In: Endocrine Research, Vol. 30, No. 4, 2004, p. 617-621.

Research output: Contribution to journalArticle

Kobayashi, Sakiko ; Shibata, Hirotaka ; Yokota, Kenichi ; Suda, Noriko ; Takeda, Ayano ; Kurihara, Isao ; Saito, Ikuo ; Saruta, Takao. / FHL2, UBC9, and PIAS1 are novel estrogen receptor α-interacting proteins. In: Endocrine Research. 2004 ; Vol. 30, No. 4. pp. 617-621.
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