1. Dynein Light Chain 1, a p21-Activated Kinase 1-Interacting Substrate, Promotes Cancerous Phenotypes
- Author
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Petra den Hollander, Diep Nguyen, Ratna K. Vadlamudi, Aysegul A. Sahin, Zhibo Yang, Rozita Bagheri-Yarmand, Seetharaman Balasenthil, and Rakesh Kumar
- Subjects
Cancer Research ,Time Factors ,Apoptosis ,Mitogen-activated protein kinase kinase ,0302 clinical medicine ,Neoplasms ,Serine ,Drosophila Proteins ,ASK1 ,Phosphorylation ,Glutathione Transferase ,0303 health sciences ,Alanine ,Kinase ,Cell Cycle ,Flow Cytometry ,Immunohistochemistry ,Phenotype ,Up-Regulation ,Cell biology ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,P21 Activated Kinase 1 ,DLC1 ,Signal transduction ,Cell Division ,Plasmids ,Protein Binding ,Signal Transduction ,Cell Survival ,Blotting, Western ,Dynein ,Breast Neoplasms ,Protein Serine-Threonine Kinases ,Biology ,Immunoglobulin light chain ,03 medical and health sciences ,Cell Line, Tumor ,Two-Hybrid System Techniques ,Humans ,030304 developmental biology ,Cyclin-dependent kinase 2 ,Dyneins ,Substrate (chemistry) ,Cell Biology ,Protein Structure, Tertiary ,Microscopy, Fluorescence ,p21-Activated Kinases ,Mutation ,Cancer cell ,Cancer research ,biology.protein ,Carrier Proteins ,cGMP-dependent protein kinase - Abstract
We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.
- Published
- 2013