{"oa_version":"None","page":"155-167","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","extern":"1","status":"public","intvolume":"         9","publisher":"CSH Press","quality_controlled":"1","language":[{"iso":"eng"}],"issue":"2","year":"1995","abstract":[{"text":"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.","lang":"eng"}],"publication_identifier":{"issn":["08909369"]},"doi":"10.1101/gad.9.2.155","title":"Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1","author":[{"full_name":"de Bono, Mario","last_name":"de Bono","orcid":"0000-0001-8347-0443","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","first_name":"Mario"},{"first_name":"D.","full_name":"Zarkower, D.","last_name":"Zarkower"},{"last_name":"Hodgkin","full_name":"Hodgkin, J.","first_name":"J."}],"month":"01","pmid":1,"date_updated":"2021-01-12T08:06:29Z","volume":9,"_id":"6162","external_id":{"pmid":["7851791"]},"date_published":"1995-01-15T00:00:00Z","publication":"Genes and Development","date_created":"2019-03-21T11:57:40Z","day":"15","publication_status":"published","citation":{"apa":"de Bono, M., Zarkower, D., &#38; Hodgkin, J. (1995). Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1. <i>Genes and Development</i>. CSH Press. <a href=\"https://doi.org/10.1101/gad.9.2.155\">https://doi.org/10.1101/gad.9.2.155</a>","chicago":"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.” <i>Genes and Development</i>. CSH Press, 1995. <a href=\"https://doi.org/10.1101/gad.9.2.155\">https://doi.org/10.1101/gad.9.2.155</a>.","mla":"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.” <i>Genes and Development</i>, vol. 9, no. 2, CSH Press, 1995, pp. 155–67, doi:<a href=\"https://doi.org/10.1101/gad.9.2.155\">10.1101/gad.9.2.155</a>.","ista":"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.","short":"M. de Bono, D. Zarkower, J. Hodgkin, Genes and Development 9 (1995) 155–167.","ama":"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. <i>Genes and Development</i>. 1995;9(2):155-167. doi:<a href=\"https://doi.org/10.1101/gad.9.2.155\">10.1101/gad.9.2.155</a>","ieee":"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,” <i>Genes and Development</i>, vol. 9, no. 2. CSH Press, pp. 155–167, 1995."},"type":"journal_article"}