転写調節共役因子による生体機能制御

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タイトル別名
  • Biological Roles of Nuclear Receptor Cofactors
  • テンシャ チョウセツ キョウヤク インシ ニ ヨル セイタイ キノウ セイギョ ヘイセイ 18ネンド ニホン エイヨウ ショクリョウ ガッカイ ショウレイショウ ジュショウ
  • Young Investigator Award of the 2006's JSNFS
  • 平成18年度日本栄養・食糧学会奨励賞受賞

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Fat-soluble hormones, including food-derived vitamins A and D, regulate complex programs of gene expression via the nuclear receptor family of transcription factors. Recent studies, including some done by our group, have led to the identification of cofactor protein molecules that appear to play important roles in mediating transcription by members of the nuclear receptor family. We have shown that CREB binding protein (CBP) is able to function as a nuclear receptor cofactor, and integrate various types of cellular signaling. Moreover, we have investigated the biological roles of cofactor proteins, focusing on skeletal muscle and adipose tissue, which are important for maintaining energy balance in the human body. We showed that a nuclear receptor cofactor, PGC-1β, can bind to, and activate orphan estrogen receptor-related receptors (ERRs). Transgenic mice overexpressing PGC-1β show increased energy expenditure, and are resistant to obesity induced by a high-fat diet or by genetic abnormality. Furthermore, we showed that another cofactor, FOXO1, negatively regulates skeletal muscle mass and type I fiber gene expression, leading to impaired skeletal muscle function. Activation of FOXO1 appears to be involved in the pathogenesis of muscle atrophy. These results provide insight into the molecular basis of lifestyle-related diseases such as obesity and diabetes mellitus, and the possibility of new treatments.

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