转录调节因子TORCs的研究进展及其参与神经保护作用的展望
王家伟,邓 娟*
(中山大学第三附属医院眼科,广州510630)

摘 要:摘 要:随着基础研究的深入,人们对于cAMP反应元件结合蛋白(cAMP response element binding protein,CREB)及其家族的功能了解越来越多。在多种细胞中,这些转录因子作为效应分子介导细胞外环境变化所引起基因表达和长时程生理功能改变。在神经系统,许多胞外信号,包括细胞膜去极化、膜受体通道开放以及神经损伤等,都可以引起CREB及其家族成员分子的激活,从而引起CREB依赖的基因转录。CREB的激活及其下游基因的转录在多种复杂的发育、神经可塑性和病理过程中都具有十分重要的作用。TORCs(transducers of regulated CREB)是新近被发现的一类CREB的共激活因子,但其对CREB的精确调控机制尚不明确。目前已知TORCs可以促进CREB依赖的基因转录,并且这种增强作用不依赖于CREB丝氨酸133位点的磷酸化,而是增加CREB和其辅助因子的结合,从而实现其下游基因在启动子水平的活性增加。在神经系统的各类疾病中,CREB对于促进神经元存活、再生、细胞修复等过程具有十分重要的作用。因此,作为CREB的共激活因子,TORCs在神经损伤修复中也具有潜在作用,本文主要针对新近发现的CREB共激活因子TORCs进行简要的文献综述和其在神经保护作用中的展望。
关键词:TORCs; CREB; PGC-1; 神经保护
中图分类号:Q513.1; R741  文献标识码:

The research of transducers of regulated CREB(TORCs) and its potential role in neural protection
WANG Jia-wei, DENG Juan*
(Department of Ophthalmology, The Third Affilicated Hosipital of Sun Yat-Sen University, Guangzhou 510630, China)

Abstract: Abstract: The profound function of CREB (cAMP response element binding protein) in biological processes has been intensively studied in the last two decades. In almost all types of cells, CREB mediate the changes of gene transcription and long-term physiological adaption in response to the changes of extracellular environment. In nervous system, many extracellular signals, such as membrane depolarization, activation of receptor and ionic channels in membrane as well as neural injury lead to the activation of CREB and its downstream gene transcription, which plays significant role in many complex processes like development, plasticity, and neurological disease conditions. TORCs (transducers of regulated CREB) were recently identified as coactivators of CREB and potentiate CREB-dependent gene transcription, but the precise mechanism is unknown. Some studies indicated that TORCs working independent of phosphorylation of CREB at Ser 133. In many neurological disease conditions, CREB is critical for neuronal survival, regeneration , and so on. Thus, as a coactivator of CREB, it抯 very likely that TORCs play potential roles in neural regeneration. In this review, we briefly summarize recent progress of TORCs and prospect its potential role in neural protection.
Key words: TORCs; CREB; PGC-1; neural protection

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