IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells
Keywords:Cancer cells, signal transduction, IKKɛ (IKBKE), TPL2 (MAP3K8), MEK1 (MAP2K1), ERK1/2 (MAPK1/2)
IKBKE have been associated with numerous cancers. As a result, IKBKE have emerged as potential target for cancer therapy. Accumulating evidence support that IKBKE orchestrate tumor cell survival in cancers. Here we evaluated the possible link between IKBKE and ERK phosphorylation. The effects of IKBKE silencing on MAPK activation in tumor vs. normal cells were evaluated via WB and RT-PCR. Ectopically expressed IKBKE, TPL2 or MEK1 constructs were used to examine the possible interactions among them via co-IP. In vitro kinase assays were performed to understand nature of the observed interactions. In tumors, IKBKE regulates MEK/ERK constitutive activations in vitro and in vivo. IKBKE and TPL2 physically interact and this interaction leads to TPL2 phosphorylation. We describe here a novel regulatory link between IKBKE and constitutive ERK1/2 activation in tumor cells. This new circuitry may be relevant for tumor cell survival in various malignancies.
How to Cite
Copyright (c) 2022 Serkan İsmail Göktuna
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish in this journal agree to the following terms:
- The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
- The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
- Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
- The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).