Contribution of the amino and carboxyl termini for PHA-4/FoxA function in Caenorhabditis elegans.
FoxA transcription factors are central regulators of gut development in all animals that have been studied. Here we examine the sole Caenorhabditis elegans FoxA protein, which is called pha-4. We describe the molecular characterization of five pha-4 mutations and characterize their associated phenotypes. Two nonsense mutations are predicted to truncate PHA-4 after the DNA binding domain and remove the conserved carboxyl terminus. Surprisingly, animals harboring these mutations are viable, provided the mutant mRNAs are stabilized by inactivating the nonsense-mediated decay pathway. Two additional nonsense mutations reveal that the DNA binding domain is critical for activity. A missense mutation predicted to alter the PHA-4 amino terminus leads to a dramatic reduction in pha-4 activity even though the protein is expressed appropriately. We suggest that the PHA-4 amino terminus is essential for PHA-4 function in vivo, possibly as a transactivation domain, and can compensate for loss of the carboxyl terminus. We also provide evidence for autoregulation by PHA-4.
Kaltenbach
Linda S
LS
Huntsman Cancer Institute and Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.
Updike
Dustin L
DL
Mango
Susan E
SE
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004247:DNA / Q000737:chemistry; D006579:Heterozygote; D006720:Homozygote; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D015533:Transcriptional Activation
D029742:Caenorhabditis elegans Proteins; C113277:Pha-4 protein, C elegans; D015534:Trans-Activators; D004247:DNA