Special issue on mitogen-activated protein kinases: New insights into regulation, function and role in human disease.
Special issue on mitogen-activated protein kinases: New insights into regulation, function and role in human disease.
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关于丝裂原激活蛋白激酶的特刊：对人类疾病中的调节、功能和作用的新见解。
DOI：
10.1016/j.bbamcr.2007.03.005
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Tzivion,Guri
中科院分区：
文献类型：
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作者：
Tzivion,Guri
丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路在过去的20年里得到了广泛的研究，确立了其在众多细胞功能中的关键作用，并建立了一个模型信号通路系统。特别重要的是早期认识到它们参与各种人类癌症，促使人们共同努力，以确定沿着途径的抑制剂作为潜在的癌症治疗剂。目前，临床试验中有几种靶向各种MAPK通路的先导化合物，主要是Raf、MLK和MEK抑制剂。虽然在理解MAPK功能和调节的各个方面已经取得了显着进展，但许多其他方面仍然知之甚少。这些方面尤其包括MAPK在正常细胞生长条件下、发育期间、细胞周期调节中以及相对于不同细胞类型功能的生理作用。其他紧迫的问题涉及到定义其调控的确切分子方面，定义各种MAPK途径之间的串扰关系，以及更好地定义其下游靶点。此外，MAPK通路抑制剂在临床试验中的广泛结合以及在不久的将来可能在临床中的广泛结合要求更好地评估来自临床试验的数据的方法，以帮助设计未来的目标和方法来提高治疗效果。这份MAPKs专刊的目的是对该领域进行全面和最新的审查，同时强调我们理解中存在的问题和差距。此外，特别关注MAPK在各种病理中的作用以及我们对这些通路的靶向治疗的看法。本期的第一部分提供了该领域的历史概述，并介绍了经典的Ras-Raf-MEK-ERK MAPK通路，涵盖了从受体水平到ERK及其靶点的通路。第二部分着重于MAPK的磷酸酶调控方面，并通过串扰机制，并解决临床方面和其他新兴的新概念。第三部分涵盖了MAPK功能的生理学方面，也包括酵母MAPK的概述。最后一部分涵盖了所谓的应激激活MAPK途径，并包括非典型MAPK的审查。显然，这一不同领域的所有方面不可能在一个问题中得到解决，我们向这一领域的许多贡献者表示歉意，他们的工作没有被包括在内。
The mitogen-activated protein kinase (MAPK) signaling pathways have been extensively studied for the past 20 years, establishing their key roles in numerous cellular functions and founding a model signaling pathway system. Of special significance was the early recognition of their involvement in various human cancers, prompting a concerted effort to identify inhibitors along the pathway as potential cancer therapeutics. Currently there are several lead compounds in clinical trials that target various MAPK pathways, predominantly Raf, MLK and MEK inhibitors. Although remarkable progress has been made in understanding various aspects of MAPK function and regulation, many other remain poorly understood. These aspects include among others the physiological effects of MAPKs under normal cell growth conditions, during development, in cell cycle regulation and with respect to distinct cell type functions. Other pressing questions relate to defining the exact molecular aspects of their regulation, defining the cross-talk relationships between the various MAPK pathways and better defining their downstream targets. Furthermore, the extensive incorporation of inhibitors of MAPK pathways in clinical trials and potentially in the near future in the clinic calls for ways to better evaluate the data coming from clinical trials to help in designing future targets and approaches to improving treatment efficacy. The aim of this MAPKs-dedicated special issue is to provide a comprehensive and up-to-date review of the field while underlining the remaining questions and gaps in our understanding. In addition, a special focus is given to the role of MAPKs in various pathologies and our perceptions regarding the targeting of these pathways for therapy.The first part of this issue provides a historical overview of the field and introduces the classical Ras-Raf-MEK-ERK MAPK pathway, covering the pathway from the receptor level to ERKs and their targets. The second part focuses on aspects of MAPK regulation by phosphatases and through cross-talk mechanisms and addresses clinical aspects and other emerging novel concepts. The third part covers physiological aspects of MAPK function and also includes an overview of yeast MAPKs. The final part covers the so-called stress-activated MAPK pathways and includes a review of atypical MAPKs. Obviously, not all aspects of this diverse field could be addressed in one issue, and we extend our apologies to the many contributors to this field whose work was not covered.