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 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.

Automated summary

IKBKE is associated with various cancers and has emerged as a potential target for cancer therapy. It orchestrates tumor cell survival by regulating MEK/ERK activation in tumors. The interaction between IKBKE and TPL2 leads to TPL2 phosphorylation, providing a novel regulatory link between IKBKE and constitutive ERK1/2 activation in tumor cells.