c-Jun N-terminal kinase (JNK) signaling: Recent advances and challenges
c-Jun N-terminal kinase (JNK) signaling: Recent advances and challenges
复制标题
DOI：
10.1016/j.bbapap.2009.11.002
复制
发表时间：
2010-03-01
影响因子：
3.2
通讯作者：
Ng, Dominic C. H.
中科院分区：
文献类型：
--
作者：
Bogoyevitch, Marie A.;Ngoei, Kevin R. W.;Ng, Dominic C. H.
C-JUN N末端激酶（JNKS）首先被描述为促丝分裂原激活蛋白激酶（MAPK）家族的应激激活成员，已成为抑制剂筛查策略的重点，该研究表明其在其在发展中的关键作用，这些策略已表明其在发展中的关键作用许多疾病，例如糖尿病，神经退行性和肝病。我们讨论了ATP竞争和ATP非竞争性JNK抑制剂的发现和开发的最新进展。由于了解这些抑制剂的作用方式并改善其性质将取决于对JNK结构，JNK催化机制和底物的更好理解，因此也考虑了JNK生物化学领域的最新进展。此外，使用JNK基因敲除动物的使用正在继续揭示这些激酶的体内功能，而组织特异性的作用现在用组织特异性的敲除。这些最新进展突出了现在面临的许多挑战，特别是在特定组织中JNK同工型的定向靶向中。 （c）2009 Elsevier B.V.保留所有权利。
c-Jun N-terminal kinases (JNKs), first characterized as stress-activated members of the mitogen-activated protein kinase (MAPK) family, have become a focus of inhibitor screening strategies following studies that have shown their critical roles in the development of a number of diseases, such as diabetes, neurodegeneration and liver disease. We discuss recent advances in the discovery and development of ATP-competitive and ATP-noncompetitive JNK inhibitors. Because understanding the modes of actions of these inhibitors and improving their properties will rely on a better understanding of JNK structure, JNK catalytic mechanisms and substrates, recent advances in these areas of JNK biochemistry are also considered. In addition, the use of JNK gene knockout animals is continuing to reveal in vivo functions for these kinases, with tissue-specific roles now being dissected with tissue-specific knockouts. These latest advances highlight the many challenges now faced, particularly in the directed targeting of the JNK isoforms in specific tissues. (C) 2009 Elsevier B.V. All rights reserved.