The tumor suppressor LKB1 induces p21 expression in collaboration with LMO4, GATA-6, and Ldb1.
The LKB1/STK11 serine/threonine kinase is mutated in Peutz-Jeghers syndrome and various sporadic cancers such as lung adenocarcinoma. We show here that LKB1 forms a complex with LMO4, GATA-6, and Ldb1, and enhances GATA-mediated transactivation in a kinase-dependent manner. We further demonstrate that LKB1 has the potential to induce p21 expression in collaboration with LMO4, GATA-6, and Ldb1 through the p53-independent mechanism. Our findings suggest that LKB1 regulates GATA-mediated gene expression and that this activity of LKB1 may be important for its tumor suppressor function.
Setogawa
Takeshi
T
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Shinozaki-Yabana
Satoko
S
Masuda
Takahisa
T
Matsuura
Ken
K
Akiyama
Tetsu
T
D000091162:AMP-Activated Protein Kinase Kinases; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050993:GATA6 Transcription Factor / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; D018398:Homeodomain Proteins; C486312:LDB1 protein, human; D060588:LIM Domain Proteins; C114905:LMO4 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases