Options
MST Kinases Monitor Actin Cytoskeletal Integrity and Signal via c-Jun N-Terminal Kinase Stress-Activated Kinase To Regulate p21Waf1/Cip1 Stability
Author(s)
Date Issued
2009-10-12
Date Available
2014-05-02T09:05:11Z
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 p21Waf1/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.
Type of Material
Journal Article
Publisher
American Society for Microbiology
Journal
Molecular and Cellular Biology
Volume
29
Issue
24
Start Page
6380
End Page
6390
Copyright (Published Version)
2009 American Society for Microbiology
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
File(s)
Owning collection
Scopus© citations
69
Acquisition Date
Mar 28, 2024
Mar 28, 2024
Views
1506
Last Month
1
1
Acquisition Date
Mar 28, 2024
Mar 28, 2024
Downloads
411
Last Month
3
3
Acquisition Date
Mar 28, 2024
Mar 28, 2024