Ssdp proteins bind to LIM-interacting co-factors and regulate the activity of LIM-homeodomain protein complexes in vivo

Author:

van Meyel Donald J.12,Thomas John B.1,Agulnick Alan D.34

Affiliation:

1. The Salk Institute for Biological Studies, PO Box 85800, San Diego, CA 92186,USA

2. Present address: McGill University Centre for Research in Neuroscience, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada

3. Department of Biology, University of California, Riverside, CA 92521,USA

4. Present address: CyThera, San Diego, CA 92121, USA

Abstract

LIM-homeodomain transcription factors control a variety of developmental processes, and are assembled into functional complexes with the LIM-binding co-factor Ldb1 (in mouse) or Chip (in Drosophila). We describe the identification and characterization of members of the Ssdp family of proteins,which we show to interact with Ldb1 and Chip. The N terminus of Ssdp is highly conserved among species and binds a highly conserved domain within Ldb1/Chip that is distinct from the domains required for LIM binding and self-dimerization. In Drosophila, Ssdp is expressed in the developing nervous system and imaginal tissues, and it is capable of modifying the in vivo activity of complexes comprised of Chip and the LIM-homeodomain protein Apterous. Null mutations of the ssdp gene are cell-lethal in clones of cells within the developing wing disc. However, clones mutant for a hypomorphic allele give rise to ectopic margins, wing outgrowth and cell identity defects similar to those produced by mutant clones of Chipor apterous. Ssdp and Ldb/Chip each show structural similarity to twoArabidopsis proteins that cooperate with one another to regulate gene expression during flower development, suggesting that the molecular interactions between Ssdp and Ldb/Chip proteins are evolutionarily ancient and supply a fundamental function in the regulated control of transcription.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

Reference54 articles.

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2. Bach, I., Carriere, C., Ostendorff, H. P., Andersen, B. and Rosenfeld, M. G. (1997). A family of LIM domain-associated cofactors confer transcriptional synergism betwwn LIM and Otx homeodomain proteins. Genes Dev.11,1370-1380.

3. Bayarsaihan, D., Soto, R. J. and Lukens, L. N.(1998). Cloning and characterization of a novel sequence-specific single-stranded-DNA-binding protein. Biochem J.331,447-452.

4. Blair, S. S., Brower, D. L., Thomas, J. B. and Zavortink, M.(1994). The role of apterous in the control of dorsoventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila.Development120,1805-1815.

5. Brand, A. H. and Perrimon, N. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development118,401-415.

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