THE ETS TRANSCRIPTION FACTOR ER81

The ER81 protein belongs to the ETS class of DNA-binding transcription factors. It is stimulated by oncoproteins such as Ras and HER2/Neu that induce in vivo phosphorylation of ER81 via MAP kinase signaling pathways. In addition, Ras and HER2/Neu stimulate the acetyltransferase activity of the coactivator p300 which in turn promotes ER81-dependent transcription through acetylation of ER81 and histones.

We have identified several ER81 target genes, whose dysregulation is involved in cancer formation. These include hTERT, the catalytic subunit of telomerase which is required for immortalization of the vast majority of cancer cells; Smad7, an inhibitor of TGF-beta-mediated tumor surveillance; MMP-1, a metalloproteinase involved in tumor invasion and metastasis; and Rcl, a hitherto scarcely characterized putative oncoprotein. Collectively, our results have established that ER81 is an important downstream effector of several oncoproteins in many different tumors.

In the future, we would like to unravel the consequences of ubiquitylation and sumoylation on ER81 function, study how other transcription factors interfere with ER81 activity, characterize how tumor suppressing signaling pathways inhibit ER81 function, and analyze the physiological functions of Rcl.