Effect of S127A mutation of ZBTB5 on gene expression in TNFa-treated murine B16F10 melanoma cells
Activation of mTORC1 is crutial for tumorigenesis. Here we identify ZBTB5 as an evolutionarily arisen regulator to translate inflammatory signals to activate mTORC1 pathway in the  tumor microenvironment. Mechanistically, inflammatory cytokine TNFa promotes phosphorylation of ZBTB5-S127 confering ZBTB5 as an adaptor to recruit the E3 ubiquitin ligase Cullin3 to activate mTORC1 signaling and promote tumorigenesis. Thus, disrupting inflammation-induced mTORC1 activity represents a promising therapeutic vulnerability of tumor. Overall design: To investigate the effect of the ZBTB5-S127 phosphorylation on the inflammtion-induced mTORC1 activation, we established the ZBTB5-S127A B16F10 cell line in which ZBTB5-S127 phosphorylation is silenced. We then performed gene expression profiling analysis using data obtained from RNA-seq of TNFa-treated ZBTB5-S127A and wild-type control B16F10 cell. Comparative gene expression profiling analysis of RNA-seq data for the ZBTB5-S127A cells and its wild-type control cells.