IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells
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 IKB...
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| Format: | Article |
| Language: | English |
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IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
2022-02-01
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| Series: | EXCLI Journal : Experimental and Clinical Sciences |
| Subjects: | |
| Online Access: | https://www.excli.de/index.php/excli/article/view/4578 |
| _version_ | 1797843508643495936 |
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| author | Serkan Ismail Göktuna |
| author_facet | Serkan Ismail Göktuna |
| author_sort | Serkan Ismail Göktuna |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T17:06:22Z |
| format | Article |
| id | doaj.art-61f437f8d8724caf8f6e5af7c053c9a1 |
| institution | Directory Open Access Journal |
| issn | 1611-2156 |
| language | English |
| last_indexed | 2024-04-09T17:06:22Z |
| publishDate | 2022-02-01 |
| publisher | IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund |
| record_format | Article |
| series | EXCLI Journal : Experimental and Clinical Sciences |
| spelling | doaj.art-61f437f8d8724caf8f6e5af7c053c9a12023-04-20T13:27:01ZengIfADo - Leibniz Research Centre for Working Environment and Human Factors, DortmundEXCLI Journal : Experimental and Clinical Sciences1611-21562022-02-012143645310.17179/excli2021-45784017IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cellsSerkan Ismail Göktuna0https://orcid.org/0000-0001-6169-768XDepartment of Molecular Biology and Genetics, Bilkent University, 06800 Bilkent, Ankara, Turkey. E-mail: serkan.goktuna@bilkent.edu.trIKBKE 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.https://www.excli.de/index.php/excli/article/view/4578cancer cellssignal transductionikkɛ (ikbke)tpl2 (map3k8)mek1 (map2k1)erk1/2 (mapk1/2) |
| spellingShingle | Serkan Ismail Göktuna IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells EXCLI Journal : Experimental and Clinical Sciences cancer cells signal transduction ikkɛ (ikbke) tpl2 (map3k8) mek1 (map2k1) erk1/2 (mapk1/2) |
| title | IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells |
| title_full | IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells |
| title_fullStr | IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells |
| title_full_unstemmed | IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells |
| title_short | IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells |
| title_sort | ikbke driven tpl2 and mek1 phosphorylations sustain constitutive erk1 2 activation in tumor cells |
| topic | cancer cells signal transduction ikkɛ (ikbke) tpl2 (map3k8) mek1 (map2k1) erk1/2 (mapk1/2) |
| url | https://www.excli.de/index.php/excli/article/view/4578 |
| work_keys_str_mv | AT serkanismailgoktuna ikbkedriventpl2andmek1phosphorylationssustainconstitutiveerk12activationintumorcells |