Author/Authors :
Vadlamudi، نويسنده , , Ratna K and Bagheri-Yarmand، نويسنده , , Rozita and Yang، نويسنده , , Zhibo and Balasenthil، نويسنده , , Seetharaman and Nguyen، نويسنده , , Diep and Sahin، نويسنده , , Aysegul A and den Hollander، نويسنده , , Petra and Kumar، نويسنده , , Rakesh، نويسنده ,
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 Pak1ʹs 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.
