Studies on the interactions of Cten with β-catenin and α-actinin4 and the molecular mechanism underlying nucleocytoplasmic shuttling of Cten

• Main Authors: Derrick Lee, 李昌恆
• Other Authors: 廖憶純
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/rwc22v

碩士 === 國立臺灣大學 === 生化科技學系 === 102 === C-terminal tensin-like protein (Cten) locates in focal adhesion complex and participates in regulating cell adhesion and migration. Elevated Cten level has been detected in all stage of colon cancers. Furthermore, a high population of Cten is located in the nucleus. Therefore, nuclear Cten may play an important role in colon cancer cell progression. In this study, we demonstrated that Cten interacts with β-catenin and α-actinin4 in the nucleus. Cten indirectly interacts with β-catenin. Whereas α-actinin4 associates with C-terminal half of Cten (327~715) through its N- and C-terminal domain. The interactions of Cten, β-catenin and α-actinin4 may not be required for the nuclear targeting of each protein. Using the qPCR, we showed that nuclear Cten may not participate in regulating α-actinin4 -mediated NFκB downstream genes expression. In elucidating the molecular mechanism underlying nucleocytoplasmic shuttling of Cten, we found that Cten may translocate to the nucleus through its SH2-PTB domain and is exported by the chromosome region maintenance-1 (CRM-1) dependent pathway. In silico analysis by two NES database shows that Cten contains nuclear export signal (NES) between 102 to 118 amino acid residues. Deletion in putative NES of Cten results in its nucleus retention. These findings provide possible molecular mechanisms for nucleocytoplasm shuttling of Cten.