Phorbolエステル誘導性遺伝子は,TPA調節されたトランス作用因子によって認識される共通のcis要素を含んでいます
Cell
|June 19, 1987
まとめ
Phorbolエステル腫瘍プロモーターは,転写因子AP-1によって認識される保存されたDNAモチーフを通じて遺伝子発現を活性化します. この結合活動はTPA治療後に急速に増加し,AP-1を示す.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- 細胞シグナル伝達 細胞信号伝達
背景:
- TPAのようなPhorbolエステルは,遺伝子発現に影響を与える腫瘍プロモーターとして知られています.
- いくつかのTPA誘導性遺伝子は,プロモーター領域で共通のDNA配列モチーフを共有しています.
研究 の 目的:
- TPA誘導性に関与するDNA要素を特定する.
- これらの元素に結合する転写因子を決定する.
- TPA誘発の遺伝子活性化のメカニズムを解明する.
主な方法:
- TPA誘導性遺伝子プロモーターにおける保存されたDNAモチーフの分析.
- 合成プロモーター・レポーター遺伝子構造の構築.
- DNaseの足跡測定は,タンパク質とDNAの相互作用を特定するために行われます.
- DNAモチーフの役割を評価するためのサイト指向型変異.
主要な成果:
- 保存された9bpモチーフ (TPA反応性元素,TRE) は,TPA誘導性遺伝子プロモーターで特定されました.
- 合成のTREは,異質なプロモーターにTPA誘導性を授与した.
- 転写因子AP-1はTRE.と結合する.
- TREの突然変異は,基礎およびTPA誘発の活性とAP-1結合の両方を廃止しました.
- TPA治療は,翻訳後のメカニズムを通じてTRE結合活性を急速に増加させました.
結論:
- AP-1は,TPAが遺伝子発現に与える影響を媒介する重要な転写因子である.
- TREはAP-1と結合し,TPA誘導性を授与する機能的なDNA要素です.
- TPAシグナル伝達経路はAP-1に収束し,遺伝子転写が強化される.
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