Cdx-Hox protein interactions

Abstract

Cdx and Hox gene families both code for homeodomain-containing transcription factors and both are required for proper patterning of the anterior-posterior axis. Although Cdx is known to be upstream of certain Hox genes, preliminary data indicated Cdx1 interacts in vitro with Hoxd4 but not Hoxa9, and that this interaction is localized to the C-terminal region of both proteins. GST-pulldown assays with in vitro radiolabelled proteins or transfected cell lysates were used to investigate the extent of the Cdx-Hox interactions. The interaction was narrowed down to specific residues in the first half of the homeodomain, but an inhibitory N-terminus can abrogate interaction in vitro. A larger group of Hox proteins interact with GST-Cdx when they are expressed in a cellular environment. This could mean that the interaction requires other cofactors, such as Hox cofactors Pbx and Meis that also interact with GST-Cdx1 in vitro. This study is the first example of Cdx-Hox protein interactions and suggests that the Cdx-Hox complex could be involved in the regulation of downstream Hox target genes.