title: Dimerization-driven degradation of C. elegans and human E proteins.
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.
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA; Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA;
authors.forename: Maria D
authors.initials: MD
authors.lastname: Sallee
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA; Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA; Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Iva
authors.initials: I
authors.lastname: Greenwald
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002478:Cells, Cultured; D019281:Dimerization; D015536:Down-Regulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D059748:Proteolysis; D014599:Uterus / Q000196:embryology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins
keywords: C. elegans; E2A; HLH-2; TCF3; bHLH