SRC-3コアクティベーターの機能寿命は,リン酸に依存したユビキチン時間時計によって調節されます
Ray-Chang Wu1, Qin Feng, David M Lonard
1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Cell
|June 19, 2007
まとめ
SRC-3 (ステロイド受容体共同活性化剤-3) の規制されたユビキチン化は,その活性化と分解を制御する. このリン酸化に依存するプロセスは"転写時間時計"として機能し,コアクティベーター機能をバランスさせ,腫瘍生成を防止します.
科学分野:
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
- がん研究 がん研究
背景:
- SRC-3 (ステロイド受容体コアクティベーター-3) /AIB1は,過剰活性化すると,腫瘍発生に関与する重要な成長コアクティベーターです.
- SRC-3の活性を厳密に調節することは,正常な細胞機能と制御不能な成長を防ぐために不可欠です.
研究 の 目的:
- SRC-3コアクティベーターの活性化と転写特異性に関する規制メカニズムを解明する.
- SRC-3の機能と安定性の制御における,リン酸化依存性ユビキチネーションの役割を調査する.
主な方法:
- SRC-3内の重要な"アクロン/デグロン"要素の識別.
- GSK3を責任キナーゼとして,SCF ((Fbw7alpha)) をE3ユビキチンリガゼとして特徴づけました.
- SRC-3のユビキチネーションパターン (マルチ/モノ・ユビキチネーション対ポリユビキチネーション) とその機能的結果の分析.
主要な成果:
- SRC-3を調節する,リン酸化依存のユビキチネーション経路を発見した.
- GSK3とSCF ((Fbw7alpha) をこの規制カスケードで特定しました.
- SCF ((Fbw7alpha) がSRC-3の非プロテオリチス活性化とプロテオソーム分解の両方を媒介することを示した.
- 活性化から分解へと移行する二相的ユビキチネーションプロセスを観察し",転写時間時計"として作用した.
結論:
- 調整されたリン酸化とユビキチネーションは,SRC-3の活性と寿命を厳しく調節する.
- SRC-3ユビキチネーションは,コアクティベーターの活性化と分解を制御する二相イベントです.
- この規制メカニズムは,トランスクリプションの共同活性化を正確に制御し,腫瘍性過剰活性化を防止します.
関連する概念動画
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...


