Transcriptional co-activation functions of Msx homeodomain proteins by activating Hsf proteins

[摘要] The importance of Msx genes in regulating development of ocular, neuronal, cardiac, ectodermal and oro-craniofacial structures has been well established. Previous studies have shown that Msx proteins regulate gene transcription predominantly through repression by forming transcriptionally inactive heteromeric complexes. In contrast to their known suppressor activities, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression requires functional Msx proteins. Here we present data demonstrating for the first time that Msx proteins function as activators of transcription by controlling the intracellular distribution and by modulating the transcriptional activity of partnering molecules. Msx proteins activate the Hsp70 promoter through a mechanism in which Msx protein physically interacts with and modify Heat shock transcriptional factors (Hsfs) to facilitate their nuclear translocation, accumulation and subsequent transcriptional activation. The fact that Msx1 and Msx2 can stimulate Hsf mediated transcriptional activation of Hsp70 promoter in the absence of chemical, physical or physiological stress suggests that Msx1 and Msx2 may provide a critical and novel pathway in activating Hsf1 and Hsf2 and hence transcriptional induction of their target genes under normal physiological conditions.

[发布机构] University of Southern California . Libraries