期刊
CELL RESEARCH
卷 20, 期 1, 页码 99-108出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2009.141
关键词
LKB1; AMPK; Bcl-XL; thymocyte; survival; development
类别
资金
- National Natural Science Foundation of China [30872290, 30925031]
- Ministry of Science and Technology [2006CB504303, 2007CB815802, 2009ZX10004-105]
- Hi-Tech Research and Development Program of China [2007AA02Z167]
- National Basic Research Program of China [2007CB914504]
- Chinese Academy of Sciences [KSCX1-YW-R-43, KSCX2-YW-R-10]
LKB1 is a serine/threonine kinase that directly activates the energy sensor AMP-activated protein kinase (AMPK) in response to bioenergetic stress, and mainly acts as a tumor suppressor that controls cell polarity and proliferation. Although LKB1 is expressed in multiple tissues including the thymus and the spleen, its roles in T-cell development and function remain unknown. Here, we show that T-cell-specific deletion of LKB1 resulted in reduced survival of double-positive (DP) thymocytes and impaired generation of both CD4 and CD8 single-positive thymocytes. Disruption of LKB1 not only prevented the activation of AMPK but also impaired the expression of anti-apoptotic protein Bcl-XL. Importantly, ectopic expression of either Bcl-XL or the constitutively active AMPK mutant significantly rescued DP thymocytes from LKB1 deficiency-induced cell death. Moreover, ectopic expression of the constitutively active AMPK mutant was found to restore the expression of Bcl-XL in LKB1-deficient DP thymocytes. These findings identify LKB1 as a critical factor for the survival of DP thymocytes through regulation of AMPK activation and Bcl-XL expression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据