The C. elegans sex-determining GLI protein TRA-1A is regulated by sex-specific proteolysis.
TRA-1A is the sole representative in Caenorhabditis elegans of the Gli transcription factor family. Its activity is required to specify all somatic female cell fates in XX hermaphrodites. We have found that TRA-1 protein levels are much higher in hermaphrodites than in males, and that the difference is attributable to the predominance in hermaphrodites of C-terminally truncated isoforms that are nearly undetectable in males. Our results support a model in which TRA-1A is negatively regulated by male-specific proteolysis that depends upon specific TRA-1A protein sequences and upon the activity of the fem genes. C-terminally truncated TRA-1 isoforms are stable and can inappropriately feminize XO males, suggesting that they escape this negative regulation. Thus, although C. elegans appears to lack a Hedgehog-signaling pathway, our results indicate that proteolytic processing and degradation of Gli family transcription factors, commonly seen during Hedgehog signaling in other organisms, also control C. elegans sex determination.
Schvarzstein
Mara
M
Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Spence
Andrew M
AM
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012734:Disorders of Sex Development; D005260:Female; D006868:Hydrolysis; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational; D019849:Sex Determination Processes; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071676:Zinc Finger Protein GLI1
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; D020033:Protein Isoforms; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C121025:tra-1 protein, C elegans