Interaction of tRNA with MEK2 in pancreatic cancer cells.
Although the translational function of tRNA has long been established, extra translational functions of tRNA are still being discovered. We previously developed a computational method to systematically predict new tRNA-protein complexes and experimentally validated six candidate proteins, including the mitogen-activated protein kinase kinase 2 (MEK2), that interact with tRNA in HEK293T cells. However, consequences of the interaction between tRNA and these proteins remain to be elucidated. Here we tested the consequence of the interaction between tRNA and MEK2 in pancreatic cancer cell lines. We also generated disease and drug resistance-derived MEK2 mutants (Q60P, P128Q, S154F, E207K) to evaluate the function of the tRNA-MEK2 interaction. Our results demonstrate that tRNA interacts with the wild-type and mutant MEK2 in pancreatic cancer cells; furthermore, the MEK2 inhibitor U0126 significantly reduces the tRNA-MEK2 interaction. In addition, tRNA affects the catalytic activity of the wild type and mutant MEK2 proteins in different ways. Overall, our findings demonstrate the interaction of tRNA with MEK2 in pancreatic cancer cells and suggest that tRNA may impact MEK2 activity in cancer cells.
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Xiaoyun
X
Wang
Department of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Christina R
CR
Chow
Department of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Kazumi
K
Ebine
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
Jiyoung
J
Lee
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
Marsha R
MR
Rosner
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Tao
T
Pan
Department of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Hidayatullah G
HG
Munshi
D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012343:RNA, Transfer / Q000378:metabolism*
D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D012343:RNA, Transfer; C482128:MAP2K2 protein, human; D048370:MAP Kinase Kinase 2