The conserved glutamine-rich region of chick csal1 and csal3 mediates protein interactions with other spalt family members. Implications for Townes-Brocks syndrome.
Members of the spalt family of zinc finger-containing proteins have been implicated in development and disease. However, very little is known about the molecular function of spalt proteins. We have used biochemical approaches to characterize functional domains of two chick spalt homologs, csal1 and csal3. We show that csal1 and csal3 proteins repress transcription and that they can interact with each other. Furthermore, we found that truncated chick spalt proteins, similar to the truncated spalt protein expressed in the human congenital disorder Townes-Brocks syndrome, affect the nuclear localization of full-length spalt. Our findings have implications for the understanding of Townes-Brocks syndrome and the role of spalt genes in normal development. We propose that truncated spalt can exert a dominant negative effect and is able to interfere with the correct function of full-length protein, by causing its displacement from the nucleus. This could affect the transcriptional repressor activity of spalt and DNA binding. Spalt protein truncations could also affect the function of other spalt family members in various tissues.
Sweetman
Dylan
D
School of Biological Sciences, University of East Anglia, Norwich, Norfolk NR4 7TJ, United Kingdom.
Smith
Terry
T
Farrell
Elizabeth R
ER
Chantry
Andrew
A
Munsterberg
Andrea
A
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D017124:Conserved Sequence; D004195:Disease Models, Animal; D005121:Extremities / Q000196:embryology; D005973:Glutamine; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013577:Syndrome; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D029867:Xenopus Proteins; D016335:Zinc Fingers
D018398:Homeodomain Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D011994:Recombinant Proteins; C484466:SALL3 protein, human; D014157:Transcription Factors; D029867:Xenopus Proteins; C103405:sal1-A protein, Xenopus; C484468:spalt protein, vertebrate; D005973:Glutamine