Association of LKB1 with a WD-repeat protein WDR6 is implicated in cell growth arrest and p27Kip1 induction
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Germline mutations of the serine/threonine kinase LKB1 (also known as STK11) lead to Peutz–Jeghers syndrome (PJS) that is associated with increased incidence of malignant cancers. However, the tumor suppressor function of LKB1 has not been fully elucidated. We applied yeast two-hybrid screening and identified that a novel WD-repeat protein WDR6 was able to interact with LKB1. Immunofluorescence staining revealed that WDR6 was localized in cytoplasm, similar to the localization of LKB1. Expression of LKB1 was able to inhibit colony formation of Hela cells. Interestingly, coexpression of WDR6 with LKB1 enhanced the inhibitory effect of LKB1 on Hela cell proliferation. Consistently, WDR6 was able to synergize with LKB1 in cell cycle G1 arrest in Hela cells. Coexpression of WDR6 and LKB1 was able to induce a cyclin-dependent kinase (CDK) inhibitor p27Kip1. Furthermore, the stimulatory effect of LKB1 on p27Kip1 promoter activity was significantly elevated by coexpression with WDR6. Collectively, these results provided initial evidence that WDR6 is implicated in the cell growth inhibitory pathway of LKB1 via regulation of p27Kip1.
KeywordsLKB1 WDR6 Cell cycle Tumor suppressor p27Kip1 Peutz–Jeghers syndrome WD-repeat
AMP-activated protein kinase
Cyclin-dependent kinase inhibitors
Enhanced green fluorescence protein
G proteins β subunit
We wish to thank Dr. Mackintosh at Dundee, UK for providing the human LKB1 plasmid. This work was supported by research grants from Chinese Academy of Sciences (One Hundred Talents program), National Natural Science Foundation of China (30470870 and 30588002), and Science & Technology Commission of Shanghai Municipality (05DJ14009 and 04DZ14007) to YC.
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