Association of LKB1 with a WD-repeat protein WDR6 is implicated in cell growth arrest and p27(Kip1) induction.
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 p27(Kip1). Furthermore, the stimulatory effect of LKB1 on p27(Kip1) 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 p27(Kip1).
Xie
Xiaoduo
X
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Wang
Zhenzhen
Z
Chen
Yan
Y
D000091162:AMP-Activated Protein Kinase Kinases; D002453:Cell Cycle / Q000502:physiology*; D048708:Cell Growth Processes; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C412604:WDR6 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases