Downregulation of vertebrate Tel (ETV6) and Drosophila Yan is facilitated by an evolutionarily conserved mechanism of F-box-mediated ubiquitination.

Molecular and Cellular Biology
M Guy RoukensDavid A Baker

Abstract

The vertebrate Ets transcriptional repressor Tel (ETV6) and its invertebrate orthologue, Yan, are both indispensable for development, and they orchestrate cell growth and differentiation by binding to DNA, thus inhibiting gene expression. To trigger cell differentiation, these barriers to transcriptional activation must be relieved, and it is established that posttranslational modifications, such as phosphorylation and sumoylation, can specifically impair the repressive functions of Tel and Yan and are crucial for modulating their transcriptional activity. To date, however, relatively little is known about the control of Tel and Yan protein degradation. In recent years, there has been a concentrated effort to assign functions to the large number of F-box proteins encoded by both vertebrate and invertebrate genomes. Here, we report the identification and characterization of a previously unreported, evolutionarily conserved F-box protein named Fbl6. We isolated both human and Drosophila melanogaster fbl6 cDNA and show that the encoded Fbl6 protein binds to both Tel and Yan via their SAM domains. We demonstrate that both Tel and Yan are ubiquitinated, a process which is stimulated by Fbl6 and leads to proteasomal degradation. We r...Continue Reading

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Citations

Sep 14, 2010·Nature Cell Biology·M Guy RoukensDavid A Baker
Aug 14, 2012·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Wen DuiRenjie Jiao
Feb 4, 2009·Best Practice & Research. Clinical Gastroenterology·Andre BoonstraHarry L A Janssen
Apr 20, 2010·The Journal of Biological Chemistry·Sean M GreenBarbara J Graves
Nov 19, 2017·The Journal of Biological Chemistry·David G P van IJzendoornDavid A Baker
Feb 12, 2021·Cell Death and Differentiation·Yajun LiYoujun Li
Jun 3, 2021·International Journal of Molecular Sciences·Charles Ducker, Peter E Shaw

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