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

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

研究成果: Article査読

42 被引用数 (Scopus)


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.

ジャーナルEndocrine Research
出版ステータスPublished - 2004

ASJC Scopus subject areas

  • 内分泌学


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