Direct protein-protein interaction between the intracellular domain of TRA-2 and the transcription factor TRA-1A modulates feminizing activity in C. elegans.
In the nematode Caenorhabditis elegans, the zinc finger transcriptional regulator TRA-1A directs XX 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 tra-1-dependent feminizing activity in somatic tissues, indicating that the interaction enhances TRA-1A activity. Consistent with this hypothesis, we show that tra-2(mx) mutations, which weakly masculinize somatic tissues, disrupt the TRA-2/TRA-1A interaction. Paradoxically, tra-2(mx) mutations feminize the XX germ line, as do tra-1 mutations mapping to the TRA-2 binding domain. We propose that these mutations render tra-2 insensitive to a negative regulator in the XX 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 XX 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).
Lum
D H
DH
Department of Molecular and Medical Genetics, University of Toronto, Toronto, M5S 1A8, Canada.
Kuwabara
P E
PE
Zarkower
D
D
Spence
A M
AM
D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D012734:Disorders of Sex Development / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018095:Germ-Line Mutation; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D017434:Protein Structure, Tertiary; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism*; D019849:Sex Determination Processes; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D015801:Helminth Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; C075059:fem-3 protein, C elegans; C121025:tra-1 protein, C elegans; C066174:tra2 protein, Drosophila