Dimerization-driven degradation of C. elegans and human E proteins |
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| Authors: | Maria D. Sallee Iva Greenwald |
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| Affiliation: | 1.Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA;;2.Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA;;3.Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA |
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| Abstract: | E proteins are conserved regulators of growth and development. We show that the Caenorhabditis elegans E-protein helix–loop–helix-2 (HLH-2) functions as a homodimer in directing development and function of the anchor cell (AC) of the gonad, the critical organizer of uterine and vulval development. Our structure–function analysis of HLH-2 indicates that dimerization drives its degradation in other uterine cells (ventral uterine precursor cells [VUs]) that initially have potential to be the AC. We also provide evidence that this mode of dimerization-driven down-regulation can target other basic HLH (bHLH) dimers as well. Remarkably, human E proteins can functionally substitute for C. elegans HLH-2 in regulating AC development and also display dimerization-dependent degradation in VUs. Our results suggest that dimerization-driven regulation of bHLH protein stability may be a conserved mechanism for differential regulation in specific cell contexts. |
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| Keywords: | TCF3 E2A HLH-2 bHLH C. elegans |
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