The cysteine-rich LIM domains inhibit DNA binding by the associated homeodomain in Isl-1.

AUTOR(ES)

Sánchez-García, I

RESUMO

Recently, a new class of homeobox genes has been identified, called LIM-homeobox genes. These genes encode proteins which have two tandemly repeated cysteine motifs, referred to as LIM domains, in addition to a homeodomain. In addition, proteins with only LIM domains have been described but the function of the LIM domain is unknown. We have analysed the function of LIM domains using Isl-1 as a representative LIM-homeodomain protein. Employing protein prepared in bacterial cells, we show that the presence of the LIM domain in Isl-1 inhibits binding of the homeodomain to its DNA target. This in vitro inhibition can be released either by denaturation/renaturation of the protein or by truncation of the LIM domains. A similar inhibition is observed in vivo using reporter constructs. In addition we show that LIM domains in a chimeric protein can inhibit binding of the Ubx homeodomain to its target. The ability of LIM domains to inhibit DNA binding by the homeodomain provides a possible basis for negative regulation of LIM-homeodomain proteins in vivo.

Documentos Relacionados

• Cysteine-rich LIM domains of LIM-homeodomain and LIM-only proteins contain zinc but not iron.
• Regulation of cysteine-rich intestinal protein by dexamethasone in the neonatal rat.
• Are cysteine-rich and COOH-terminal domains of dystrophin critical for sarcolemmal localization?
• Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains.
• The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site.