We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Cdk inhibitor p57<sup>Kip2</sup> controls LIM-kinase 1 activity and regulates actin cytoskeleton dynamics.
- Authors
Vlachos, P.; Joseph, B.
- Abstract
The cyclin-dependent kinase inhibitor p57Kip2 gene has been suggested to be a tumor suppressor gene, being inactivated in various cancer types, linked to tumor progression and poor patient outcome. Here, we report that p57Kip2 interacts with the actin cytoskeleton modifying enzyme, LIM-kinase 1 (LIMK-1) but not LIMK-2. This interaction enhances activity of LIMK-1, independently of its activator Rho-associated kinase. This resulted in an increased phosphorylation and consequent inactivation of the actin depolymerization factor, cofilin. In accordance, selective p57Kip2 expression promotes actin stress fiber formation in cancer cells. Fluorescence recovery after photobleaching analysis of fluorescent-labeled actin further demonstrated that p57Kip2 expression results in reduction of actin protein mobile fraction, which affects its turnover rate in cell. Finally, we present evidence that the p57Kip2 control of LIMK-1 ultimately affects cell mobility negatively. Thus, in addition to its established function in control of proliferation and cell death, these results indicate that p57Kip2 is critical in the regulation of actin cytoskeleton dynamic and by this means migration ability of cancer cells.
- Publication
Oncogene, 2009, Vol 28, Issue 47, p4175
- ISSN
0950-9232
- Publication type
Academic Journal
- DOI
10.1038/onc.2009.269