Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1

M. de Bono, D. Zarkower, J. Hodgkin, Genes and Development 9 (1995) 155–167.

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Journal Article | Published | English
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Abstract
The tra-1 gene is the terminal global selector of somatic sex in Caenorhabditis elegans: High tra-1 activity elicits female somatic development while low tra-1 activity elicits male development. Previous genetic studies defined a cascade of negatively interacting genes that regulates tra-1 activity in response to the primary sex-determining signal. Here, we investigate the last step in this regulatory cascade, by studying rare gain-of-function (gf) mutations of tra-1 that direct female somatic development irrespective of the upstream sex-determining signal. These mutations appear to abolish negative regulation of tra-1 in male tissues. We identify the lesions associated with 29 of these mutations and find that all affect a short stretch of amino acid residues present in both protein products of the tra-1 gene. Twenty-six alleles are associated with single nonconservative amino acid substitutions. Two alleles affect tra-1 RNA splicing and generate messages that omit part or all of the exon encoding this short stretch. These results suggest that sexual regulation of tra-1 is achieved post-translationally, by an inhibitory protein-protein interaction. The amino acid stretch altered by the tra-1(gf) mutations may define a site of interaction for negative regulators of tra-1. The stretch includes a potential phosphorylation site for glycogen synthase kinase 3 and may be conserved in the human gene GLI3, a homolog of tra-1 identified previously.
Publishing Year
Date Published
1995-01-15
Journal Title
Genes and Development
Volume
9
Issue
2
Page
155-167
ISSN
IST-REx-ID

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de Bono M, Zarkower D, Hodgkin J. Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1. Genes and Development. 1995;9(2):155-167. doi:10.1101/gad.9.2.155
de Bono, M., Zarkower, D., & Hodgkin, J. (1995). Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1. Genes and Development, 9(2), 155–167. https://doi.org/10.1101/gad.9.2.155
Bono, Mario de, D. Zarkower, and J. Hodgkin. “Dominant Feminizing Mutations Implicate Protein-Protein Interactions as the Main Mode of Regulation of the Nematode Sex-Determining Gene Tra-1.” Genes and Development 9, no. 2 (1995): 155–67. https://doi.org/10.1101/gad.9.2.155.
M. de Bono, D. Zarkower, and J. Hodgkin, “Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1,” Genes and Development, vol. 9, no. 2, pp. 155–167, 1995.
de Bono M, Zarkower D, Hodgkin J. 1995. Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1. Genes and Development. 9(2), 155–167.
de Bono, Mario, et al. “Dominant Feminizing Mutations Implicate Protein-Protein Interactions as the Main Mode of Regulation of the Nematode Sex-Determining Gene Tra-1.” Genes and Development, vol. 9, no. 2, CSH Press, 1995, pp. 155–67, doi:10.1101/gad.9.2.155.

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