{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T16:20:46Z","timestamp":1781540446936,"version":"3.54.5"},"reference-count":57,"publisher":"Cold Spring Harbor Laboratory","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2000,12,15]]},"abstract":"<jats:p>In the nematode <jats:italic>Caenorhabditis elegans<\/jats:italic>, the zinc finger transcriptional regulator TRA-1A directs <jats:italic>XX<\/jats:italic> somatic cells to adopt female fates. The membrane protein TRA-2A indirectly activates TRA-1A by binding and inhibiting a masculinizing protein, FEM-3. Here we report that a part of the intracellular domain of TRA-2A, distinct from the FEM-3 binding region, directly binds TRA-1A. Overproduction of this TRA-1A-binding region has <jats:italic>tra-1<\/jats:italic>-dependent feminizing activity in somatic tissues, indicating that the interaction enhances TRA-1A activity. Consistent with this hypothesis, we show that<jats:italic>tra-2(mx)<\/jats:italic> mutations, which weakly masculinize somatic tissues, disrupt the TRA-2\/TRA-1A interaction. Paradoxically,<jats:italic>tra-2(mx)<\/jats:italic> mutations feminize the <jats:italic>XX<\/jats:italic> germ line, as do <jats:italic>tra-1<\/jats:italic> mutations mapping to the TRA-2 binding domain. We propose that these mutations render <jats:italic>tra-2<\/jats:italic> insensitive to a negative regulator in the <jats:italic>XX<\/jats:italic> germ line, and we speculate that this regulator targets the TRA-2\/TRA-1 complex. The intracellular domain of TRA-2A is likely to be produced as a soluble protein in vivo through proteolytic cleavage of TRA-2A or through translation of an<jats:italic>XX<\/jats:italic> germ line-specific mRNA. We further show that tagged derivatives of the intracellular domain of TRA-2 localize to the nucleus, supporting the hypothesis that this domain is capable of modulating TRA-1A activity in a manner reminiscent of Notch and Su(H).<\/jats:p>","DOI":"10.1101\/gad.853700","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T00:00:34Z","timestamp":1027728034000},"page":"3153-3165","source":"Crossref","is-referenced-by-count":209,"title":["Direct protein\u2013protein interaction between the intracellular domain of TRA-2 and the transcription factor TRA-1A modulates feminizing activity in <i>C. elegans<\/i>"],"prefix":"10.1101","volume":"14","author":[{"given":"David H.","family":"Lum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia E.","family":"Kuwabara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Zarkower","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Spence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2000,12,15]]},"reference":[{"key":"2021111419251190000_14.24.3153.1","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1002\/j.1460-2075.1992.tb05289.x","article-title":"The Caenorhabditis elegans sex determining gene fem-3 is regulated post-transcriptionally.","volume":"11","author":"Ahringer","year":"1992","journal-title":"EMBO J."},{"key":"2021111419251190000_14.24.3153.2","unstructured":"Ausubel F.M. 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