Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulation. | J. Biol. Journal of Biology BioMed Central Minireview At the crossroads AMP-activated kinase and the LKBI tumor suppressor link cell proliferation to metabolic regulation John M Kyriakis Address Molecular Cardiology Research Institute Tufts-New England Medical Center 750 Washington Street Boston MA 02111 USA. E-mail jkyriakis@ Published 22 October 2003 Journal of Biology 2003 2 26 The electronic version of this article is the complete one and can be found online at http content 2 4 26 2003 BioMed Central Ltd Abstract The tumor suppressor kinase LKB1 has been identified as a physiologic activator of the key metabolic regulator 5 -AMP-activated protein kinase establishing a possible molecular link between the regulation of metabolism and cell proliferation. The AMP-activated protein kinase AMPK is a metabolic master regulator that is activated in times of reduced energy availability high cellular AMP ATP ratios and serves to inhibit anabolic processes 1-5 . In an AMP-dependent manner AMPK phosphorylates and inhibits acetyl-CoA carboxylase ACC 1 2 the rate-limiting enzyme in fatty-acid synthesis ACC catalyzes the formation of malonyl-CoA a potent inhibitor of fatty-acid oxidation. Accordingly AMPK acts to elevate fat oxidation and reduce lipogenesis 1 2 . AMPK also catalyzes the AMP-dependent phosphorylation and inhibition of HMG-CoA reductase the rate-limiting enzyme in cholesterol biosynthesis thus reducing cholesterol formation 1 2 5 . In addition AMPK activation suppresses the expression of several lipogenic genes 2 and activates phosphofructokinase-1 thereby suppressing glucose oxidation and enhancing glycolysis the Pasteur effect . AMPK is activated in exercise where it triggers glucose uptake by skeletal muscle in an insulin-independent manner and phosphorylates and inhibits glycogen synthase 1-4 . In vivo pharmacologic activation of AMPK with 5-aminoim-idazole-4-carboxamide 1-P-D-ribofưranoside AICAR mimics exercise and triggers .
