Volume 20, No 1, Jan 2010

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 20 Issue 1, January 2010: 99-108

ORIGINAL ARTICLES

The serine/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression

Yonghao Cao*, Hai Li*, Haifeng Liu, Chao Zheng, Hongbin Ji and Xiaolong Liu

Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Correspondence: Xiaolong Liu,(liux@sibs.ac.cn)

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.

Cell Research (2010) 20:99-108. doi: 10.1038/cr.2009.141; published online 22 December 2009

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