通过非正规的异构化来整合昼夜和缺氧信号
1Department of Molecular and Cellular Biology, Scripps Research, 10550 N Torrey Pines Road, MB-21, La Jolla, CA, 92037, USA.
FEBS letters
|December 9, 2025
概括
基本的螺旋环螺旋和Per-Arnt-Sim域 (bHLH-PAS) 蛋白质,包括CLOCK,BMAL1和HIF,表现出复杂的二分化模式. 新证据表明,HIF1α和HIF2α可以与BMAL1二元化,挑战了以前的假设.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 遗传学 是一个遗传学.
背景情况:
- 基本螺旋环螺旋和Per-Arnt-Sim域 (bHLH-PAS) 蛋白质是重要的转录因子.
- 这些蛋白质被分为两个主要组,I类蛋白质通常由环境信号调节.
- 之前的研究表明,bHLH-PAS蛋白质之间存在特定的二分化限制.
研究的目的:
- 为了研究bHLH-PAS蛋白的二分化能力.
- 重新评估BMAL1和ARNT等蛋白质的假设二分化伙伴.
- 确定HIF1α和HIF2α是否可以与BMAL1.1相互作用.
主要方法:
- 对bHLH-PAS蛋白相互作用的现有文献和数据的分析.
- 关于蛋白质二分化的实验证据的审查.
- 蛋白质结构和功能域的比较分析.
主要成果:
- 以前关于bHLH-PAS蛋白质受限二分化的假设是基于有缺陷的逻辑.
- 证据支持使用BMAL1.1的低氧诱导因子 (HIF1α和HIF2α) 的二分化.
- 这一发现扩大了这些关键转录因子的已知相互作用网络.
结论:
- 对于bHLH-PAS蛋白的二分化规则比以前理解的更加灵活.
- BMAL1 可以与 CLOCK 和 HIF 蛋白质一起形成异构体.
- 这些二度化相互作用对昼夜节律和缺氧反应途径有重大影响.
相关概念视频
Circadian Rhythms and Gene Regulation
4.5K
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...
4.5K
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
Hypoxia
1.9K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
1.9K
Calmodulin-dependent Signaling
6.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.0K
Interactions Between Signaling Pathways
7.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
Non-Canonical Wnt Signaling Pathways
8.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K


