Abstract
The mitogen-activated protein kinase p38 plays key roles in cell progression, differentiation, inflammation, and apoptosis. p38 is activated by a variety of extracellular stimuli such as UV and proinflammatory cytokine tumor necrosis factor alpha (TNF-α). It has been demonstrated that destruction of microtubules with different reagents led to impaired p38 activation in response to various extracellular stimuli. However, several other groups have reported that microtubule-interfering agents stimulate the activation of MAPK superfamily members including p38 in certain cell context. The discrepancy suggests that destruction of microtubules stimulates the activation of MAPK superfamily members and thereby induces certain feedback inhibitor(s) of p38 signaling. In this article, we report that nocodazole, a widely used microtubule-interfering agent, antagonized UV- or TNF-α-induced p38 activation, even though this drug by itself weakly activated p38. The RNA synthesis inhibitor actinomycin D, but not p38-specific inhibitor SB203580, reversed the inhibitory effect of nocodazole on TNF-α-induced p38 activation. Nocodazole also weakly activated JNK, but significantly activated ERK. The inhibition by nocodazole of TNF-α-induced p38 activation was abolished by ERK-specific inhibitor U0126. Further exploration revealed that nocodazole significantly enhanced MKP-1 expression via the ERK activity. Thus, nocodazole increases the ERK activity to enhance MKP-1 expression which inhibits p38 activation induced by TNF-α.
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Acknowledgments
This study was supported by Grants from National Natural Science Foundation of China (30973547, 31100544), Key Natural Science Program of Beijing (7101008), and National Key Basic Research Program of China (2010CB911904).
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Xiangrui Guo and Xueying Zhang contributed equally to this study.
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Guo, X., Zhang, X., Li, Y. et al. Nocodazole increases the ERK activity to enhance MKP-1 expression which inhibits p38 activation induced by TNF-α. Mol Cell Biochem 364, 373–380 (2012). https://doi.org/10.1007/s11010-012-1239-5
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DOI: https://doi.org/10.1007/s11010-012-1239-5