リガンド活性化型甲状腺ホルモンおよびレチノ酸受容体は,成長因子受容体プロモーター発現を阻害する

L G Hudson¹, J B Santon, C K Glass

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla 92093.

Cell

|September 21, 1990

まとめ

甲状腺ホルモン (T3) とレチノ酸 (RA) 受容体は,成長因子遺伝子活動を抑制する. これらの受容体へのリガンド結合は,この転写抑制に不可欠であり,新しい調節機構を明らかにします.

科学分野:

分子生物学は分子生物学である.
エンドクリノロジーエンドクリノロジー
遺伝学遺伝学とは

背景:

甲状腺ホルモン (T3) とレチノ酸 (RA) は,細胞過程の重要な調節体である.
皮膜成長因子 (EGF) 受容体とc-erbB2/neuは,細胞増殖に関与する重要な成長因子受容体である.
成長因子受容体の転写的調節は複雑で,完全に理解されていません.

研究の目的:

EGF受容体とc-erbB2/neu遺伝子発現の調節におけるT3とRA受容体の役割を調査する.
T3およびRA受容体がプロモーター活性を抑制するメカニズムを解明する.
この阻害に関与するT3およびRA受容体の特定のドメインを特定する.

主な方法:

受容体-DNAの相互作用を研究するために,in vivoおよびin vitroアッセイが使用されました.
プロモーター活性は,レポーター遺伝子アッセイを用いて測定した.
T3とRA受容体の変異分析を行い,重要なドメインを特定しました.

主要な成果:

リンガンド活性化されたT3およびRA受容体は,EGF受容体およびc-erbB2/neuプロモーター活動を阻害する.
受容体は,EGF受容体遺伝子の特定の36 bpの断片に結合する.
リガンド結合領域とDNA結合領域の両方がプロモーター抑制に不可欠である.
結合された受容体と結合されていない受容体の間の競争が観察されました.

結論:

リガンド結合は,T3およびRA受容体の転写抑制機能を調節する.
これらの発見は,成長因子受容体の遺伝子発現を調節する新しいメカニズムを明らかにしています.
T3およびRA受容体は,異常な成長因子シグナル伝達を含む疾患における治療介入の潜在的な標的を代表しています.

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