Interaction of tRNA with MEK2 in pancreatic cancer cells

Xiaoyun Wang; Christina R. Chow; Kazumi Ebine; Jiyoung Lee; Marsha R. Rosner; Tao Pan; Hidayatullah G. Munshi

doi:10.1038/srep28260

Interaction of tRNA with MEK2 in pancreatic cancer cells

Xiaoyun Wang, Christina R. Chow, Kazumi Ebine, Jiyoung Lee, Marsha R. Rosner, Tao Pan^*, Hidayatullah G. Munshi

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

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.

Original language	English (US)
Article number	28260
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep28260
State	Published - Jun 15 2016

Funding

This work was supported by the Catalyst Award "Extra-translational Function of Transfer RNA as Regulators of Cellular Processes" from the Chicago Biomedical Consortium (to HGM, MRR and TP), and NIH (DP1GM105386 to TP, CA186885 to HGM).

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title = "Interaction of tRNA with MEK2 in pancreatic cancer cells",

abstract = "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.",

author = "Xiaoyun Wang and Chow, {Christina R.} and Kazumi Ebine and Jiyoung Lee and Rosner, {Marsha R.} and Tao Pan and Munshi, {Hidayatullah G.}",

note = "Funding Information: This work was supported by the Catalyst Award {"}Extra-translational Function of Transfer RNA as Regulators of Cellular Processes{"} from the Chicago Biomedical Consortium (to HGM, MRR and TP), and NIH (DP1GM105386 to TP, CA186885 to HGM).",

year = "2016",

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doi = "10.1038/srep28260",

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T1 - Interaction of tRNA with MEK2 in pancreatic cancer cells

AU - Wang, Xiaoyun

AU - Chow, Christina R.

AU - Ebine, Kazumi

AU - Lee, Jiyoung

AU - Rosner, Marsha R.

AU - Pan, Tao

AU - Munshi, Hidayatullah G.

N1 - Funding Information: This work was supported by the Catalyst Award "Extra-translational Function of Transfer RNA as Regulators of Cellular Processes" from the Chicago Biomedical Consortium (to HGM, MRR and TP), and NIH (DP1GM105386 to TP, CA186885 to HGM).

PY - 2016/6/15

Y1 - 2016/6/15

N2 - 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.

AB - 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.

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Interaction of tRNA with MEK2 in pancreatic cancer cells

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