SRFの付属タンパク質であるElk-1には,成長因子調節された転写活性化ドメインが含まれています
R Marais1, J Wynne, R Treisman
1Transcription Laboratory, Imperial Cancer Research Fund, London, England.
Cell
|April 23, 1993
まとめ
成長因子は,MAPキナーゼによって媒介されるそのリン酸化を誘発することによって,Elk-1 (転写因子) を活性化させます. このリン酸化は,c-fos血清応答要素 (SRE) を通して遺伝子転写を調節する.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- 遺伝子規制 遺伝子規制
背景:
- Elk-1とSRF転写因子の三元複合体は,c-fos血清応答要素 (SRE) に結合する.
- 成長因子刺激は,翻訳後の修正を通して,この複合体の機能に影響を与えます.
研究 の 目的:
- SREにおける転写活動の調節におけるElk-1のリン酸化の役割を調査する.
- エルク-1のリン酸化に起因するキナーゼを特定し,複雑な機能に及ぼす影響.
主な方法:
- 成長因子刺激により,三元複合体電泳運動の動きが変化する分析.
- 精製されたMAPキナーゼとElk-1を用いたインビトロリン酸化アッセイ.
- Elk-1 C端末領域によって媒介される転写活性化の評価.
主要な成果:
- 成長因子刺激は,エルク-1 C端末リン酸化とp42/p44 MAPキナーゼ活性化に関連した,三元複合体の運動性における迅速かつ可逆的な変化を引き起こす.
- MAPキナーゼによるElk-1のインビトロリン酸化は,モビリティシフトを模倣するが,形成効率を模倣しない.
- MAPキナーゼは,Elk-1のC末端領域の重要な部位をリン酸化し,これは,規制された転写活性化ドメインとしての機能に不可欠である.
結論:
- SREによる転写活性化は,SRE結合タンパク質Elk-1の成長因子調節されたリン酸化と直接関連しています.
- MAPキナーゼ媒介によるエルク-1のリン酸化は,遺伝子発現を制御する信号伝達経路における重要なステップです.
さらに関連する動画
09:07Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
06:21An Ecdysone Receptor-based Singular Gene Switch for Deliberate Expression of Transgene with Robustness, Reversibility, and Negligible Leakiness
Published on: May 7, 2018
関連する概念動画
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Eukaryotic Transcription Activators
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
