Epidermal growth factor receptor 1 (EGFR1) and its variant EGFRvIII regulate TATA-binding protein expression through distinct pathways.

Molecular and Cellular Biology
Jody FrommDeborah L Johnson

Abstract

The epidermal growth factor receptor (EGFR) family regulates essential biological processes. Various epithelial tumors are linked to EGFR overexpression or expression of variant forms, such as the EGFR1 variant, EGFRvIII. Perturbations in expression of the transcription initiation factor, TATA-binding protein (TBP), alter cellular growth properties. Here we demonstrate that EGFR1 and EGFRvIII, but not HER2, induce TBP expression at a transcriptional level through distinct mechanisms. EGFR1 enhances the phosphorylation and function of Elk-1, recruiting it to the TBP promoter. In contrast, EGFRvIII robustly induces c-jun expression, stimulating recruitment of c-fos/c-jun to an overlapping AP-1 site. Enhancing c-jun expression alone induces TBP promoter activity through the AP-1 site. To determine the underlying mechanism for differences in Elk-1 function and c-jun expression by these receptors, we inhibited the internalization of EGFR1. Persistent EGFR1 cell surface occupancy mimics EGFRvIII-mediated effects on Elk-1 and c-jun and switches the requirement of Elk-1 to AP-1 for TBP promoter induction. Together, these studies define a new molecular mechanism for the regulation of TBP expression. In addition, we identify distinct mol...Continue Reading

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Citations

Jul 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shuping Zhong, Deborah L Johnson
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Qihui ShiJames R Heath
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Mar 3, 2020·Advances in Wound Care·Gink N YangAllison J Cowin
Dec 4, 2019·BMC Bioinformatics·Ibrahim YoussefAnna Ritz

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