Densham, R., O'Neill, E., Munro, J., Konig, I., Anderson, K., Kolch, W. and Olson, M. (2009) MST Kinases Monitor Actin Cytoskeletal Integrity and Signal via c-Jun N-Terminal Kinase Stress-Activated Kinase To Regulate p21Waf1/Cip1 Stability. Molecular and Cellular Biology, 29(24), pp. 6380-6390. (doi: 10.1128/MCB.00116-09)
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Publisher's URL: http://dx.doi.org/10.1128/MCB.00116-09
Abstract
As well as providing a structural framework, the actin cytoskeleton plays integral roles in cell death, survival, and proliferation. The disruption of the actin cytoskeleton results in the activation of the c-Jun N-terminal kinase (JNK) stress-activated protein kinase (SAPK) pathway; however, the sensor of actin integrity that couples to the JNK pathway has not been characterized in mammalian cells. We now report that the mammalian Ste20-like (MST) kinases mediate the activation of the JNK pathway in response to the disruption of the actin cytoskeleton. One consequence of actin disruption is the JNK-mediated stabilization of p21(Waf1/Cip1) (p21) via the phosphorylation of Thr57. The expression of MST1 or MST2 was sufficient to stabilize p21 in a JNK- and Thr57-dependent manner, while the stabilization of p21 by actin disruption required MST activity. These data indicate that, in addition to being components of the Salvador-Warts-Hippo tumor suppressor network and binding partners of c-Raf and the RASSF1A tumor suppressor, MST kinases serve to monitor cytoskeletal integrity and couple via the JNK SAPK pathway to the regulation of a key cell cycle regulatory protein.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Munro, Dr June and Kolch, Prof Walter and Anderson, Professor Kurt and Densham, Dr Ruth and Konig, Ms Ireen and O'Neill, Mr Eric and Olson, Professor Michael |
Authors: | Densham, R., O'Neill, E., Munro, J., Konig, I., Anderson, K., Kolch, W., and Olson, M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Molecular and Cellular Biology |
ISSN: | 0270-7306 |
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