TAILIEUCHUNG - Báo cáo sinh học: "Connecting LKB1 and AMPK links metabolism with cancer"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Connecting LKB1 and AMPK links metabolism with cancer. | J. Biol. Journal of Biology BioMed Central Research news Connecting LKBI and AMPK links metabolism with cancer Pete Moore Published 29 October 2003 Journal of Biology 2003 2 24 The electronic version of this article is the complete one and can be found online at http content 2M 24 2003 BioMed Central Ltd The tumor suppressor gene product LKB1 has been identified as the upstream activating kinase for the stress-responsive AMP-activated kinase providing a link between regulators of cellular metabolism and cell proliferation in cancer. Two researchers from the University of Dundee Scotland - Grahame Hardie and Dario Alessi - have jointly solved a mystery that each had been puzzling over for several years see The bottom line box for a summary of their work . The bottom line AMP-activated protein kinase AMPK is activated in response to cellular stresses that deplete ATP but its upstream activator kinase has proved difficult to purify and characterize. Searching for the upstream kinase s that regulate s the AMPK homolog Snf1 led to the discovery of Elm1 in yeast and sequence comparisons revealed Elm1 to be a close relative of LKB1 a tumor suppressor gene product and protein kinase. Studies of LKB1 had shown its involvement in the cancer-prone Peutz-Jeghers syndrome but its downstream mode of action was unknown. LKB1 has now been identified as the upstream regulator of AMPK placing LKB1 - together with its binding partners STRAD and MO25 -in the middle of a crucial biochemical cascade that regulates cellular metabolism. This finding links the pathways controlling cellular metabolism and cell proliferation and makes LKB1 an attractive potential therapeutic target for a wide range of clinical disorders. Hardie had been looking for the upstream kinase that regulates the metabolic regulator AMP-activated kinase AMPK see the Background box while only a short walk away Alessi had been searching for the downstream target of the tumor suppressor and protein kinase LKB1.

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