Identification and characterization of a novel fushi tarazu factor 1 (FTZ-F1) nuclear receptor in Schistosoma mansoni

Changxue Lu, Wenjie Wu, Edward G. Niles, Philip T Loverde

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Fushi-tarazu factor-1 (FTZ-F1) is an orphan nuclear receptor involved in gene regulation of various developmental processes and physiological activities. We identified a new member of ftz-f1 gene in Schistosoma mansoni, termed Smftz-f1α. The Smftz-f1α gene has a complex structure with 15 exons interrupted by 14 introns. It encodes an unusually long SmFTZ-F1α protein of 1892 amino acids containing all the modular domains found in nuclear receptors. The DNA-binding domain (DBD) of SmFTZ-F1α is conserved and most similar to those of human and mouse FTZ-F1 orthologues, exhibiting a 76% identity. The ligand-binding domain (LBD) is less conserved than the DBD; it shares more diverse identity scores in different regions ranging from 23% to 42% in region II and 28% to 72% in region III. A conserved activation funtion-2 (AF-2) sequence is present in the SmFTZ-F1α LBD. This protein also contains a long hinge region (1027 aa) and an F region (220 aa) at the carboxyl end. Phylogenetic analysis suggests that SmFTZ-F1α is the orthologue of Drosophila FTZ-F1α and vertebrate NR5 members. Western blot analysis of a schistosome extract identified two proteins, one with a size (206 kDa) predicted by the SmFTZ-F1α cDNA sequence and a smaller component of 120 kDa. Smftz-f1α is expressed throughout the schistosome life cycle with the highest expression in the egg stage. SmFTZ-F1α mRNA is widely distributed in adult worms but does not appear in vitelline cells of female worms. SmFTZ-F1α localizes to a variety of tissues but is most abundant in the testis of the male and the ovary of female worms. Our results suggest that SmFTZ-F1α plays a role in regulating schistosome development and sexual differentiation similar to other FTZ-F1 family members.

Original languageEnglish (US)
Pages (from-to)25-36
Number of pages12
JournalMolecular and Biochemical Parasitology
Volume150
Issue number1
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Schistosoma mansoni
Cytoplasmic and Nuclear Receptors
Orphan Nuclear Receptors
Physiological Phenomena
Genes
Ligands
Sex Differentiation
Proteins
DNA
Life Cycle Stages
Introns
Drosophila
Ovum
Vertebrates
Testis
Ovary
Exons
Complementary DNA
Western Blotting
Amino Acids

Keywords

  • Fushi tarazu factor 1
  • Nuclear receptor
  • Schistosoma mansoni

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

Cite this

Identification and characterization of a novel fushi tarazu factor 1 (FTZ-F1) nuclear receptor in Schistosoma mansoni. / Lu, Changxue; Wu, Wenjie; Niles, Edward G.; Loverde, Philip T.

In: Molecular and Biochemical Parasitology, Vol. 150, No. 1, 11.2006, p. 25-36.

Research output: Contribution to journalArticle

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abstract = "Fushi-tarazu factor-1 (FTZ-F1) is an orphan nuclear receptor involved in gene regulation of various developmental processes and physiological activities. We identified a new member of ftz-f1 gene in Schistosoma mansoni, termed Smftz-f1α. The Smftz-f1α gene has a complex structure with 15 exons interrupted by 14 introns. It encodes an unusually long SmFTZ-F1α protein of 1892 amino acids containing all the modular domains found in nuclear receptors. The DNA-binding domain (DBD) of SmFTZ-F1α is conserved and most similar to those of human and mouse FTZ-F1 orthologues, exhibiting a 76{\%} identity. The ligand-binding domain (LBD) is less conserved than the DBD; it shares more diverse identity scores in different regions ranging from 23{\%} to 42{\%} in region II and 28{\%} to 72{\%} in region III. A conserved activation funtion-2 (AF-2) sequence is present in the SmFTZ-F1α LBD. This protein also contains a long hinge region (1027 aa) and an F region (220 aa) at the carboxyl end. Phylogenetic analysis suggests that SmFTZ-F1α is the orthologue of Drosophila FTZ-F1α and vertebrate NR5 members. Western blot analysis of a schistosome extract identified two proteins, one with a size (206 kDa) predicted by the SmFTZ-F1α cDNA sequence and a smaller component of 120 kDa. Smftz-f1α is expressed throughout the schistosome life cycle with the highest expression in the egg stage. SmFTZ-F1α mRNA is widely distributed in adult worms but does not appear in vitelline cells of female worms. SmFTZ-F1α localizes to a variety of tissues but is most abundant in the testis of the male and the ovary of female worms. Our results suggest that SmFTZ-F1α plays a role in regulating schistosome development and sexual differentiation similar to other FTZ-F1 family members.",
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