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Genes Dev. 2015 Jul 1;29(13):1356-61. doi: 10.1101/gad.261917.115.

Dimerization-driven degradation of C. elegans and human E proteins.

Author information

1
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;
2
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.

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.

KEYWORDS:

C. elegans; E2A; HLH-2; TCF3; bHLH

PMID:
26159995
PMCID:
PMC4511211
DOI:
10.1101/gad.261917.115
[Indexed for MEDLINE]
Free PMC Article

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