Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation (Mol Cell, 2008, 29:9-22)

報告日期: 2008/11/07
報告時間: 17:10/18:00
報告學生: 林秀冠
講評老師: 張敏政
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971107-3.pdf

Nuclear FAK Promotes Cell Proliferation And Survival through FERM-Enhanced p53 Degradation

Ssang-Taek Lim, Xiao Lei Chen, Yangmi Lim,1 Dan A. Hanson, Thanh-Trang Vo, Kyle Howerton, Nicholas Larocque, Susan J. Fisher, David D. Schlaepfer,and Dusko Ilic

Molecular Cell 29, 9–22, January 18, 2008

 

Speaker : 林秀冠

Commentator : 張敏政 老師

Date : 2008-11-07, 17:10-18:00

Room : 602

 

Abstract:

  Focal adhesion kinase (FAK) is a component of focal adhesion in adherent cells which is essential for embryonic development and has been implicated in several biological functions, such as survival, adhesion and cell cycle control.  Previous study demonstrated that inactivation of p53 promotes cell growth in FAK-/- fibroblasts and endothelial cells.  However, the detail mechanism of how FAK regulates p53 expression remains unclear.  The results showed that cell proliferation was reduced in E8.5 FAK-/- mouse embryos at mesoderm and this proliferation inhibition was p53 dependent. Expression of either wild type FAK or FAK FERM domain could enhance MdM2-dependent ubiquitination and proteosome degradation to control p53 expression. Binding of FAK to p53 required FERM f1 lobe and this interaction required nuclear localization of FAK. Lastly, in human diploid fibroblast cell, FAK control of cell proliferation and p53-depandent apoptosis. These results demonstrate that FAK serves as a scaffold protein in nucleus and facilitates cell proliferation and survival through regulation of p53 stability.

 

References :

1. Ilic, D., Furuta, Y., Kanazawa, S., Takeda, N., Sobue, K., Nakatsuji, N., Nomura, S., Fujimoto, J., Okada, M., Yamamoto, T., and Aizawa, S. (1995). Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539–544.

2. Ilic, D., Almeida, E.A., Schlaepfer, D.D., Dazin, P., Aizawa, S., and Damsky, C.H. (1998). Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis. J. Cell Biol. 143, 547–560.