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PKA Converts a Repressor into an Activator

Science's STKE  31 Oct 2000:
Vol. 2000, Issue 56, pp. tw11
DOI: 10.1126/stke.2000.56.tw11

HOX proteins are DNA binding transcription factors that participate in regulation of early development. Specific and high-affinity binding occur when HOX proteins form hetero-oligomeric complexes with other proteins, such as members of the PBC family of homeodomain-containing proteins. Genetic and molecular evidence suggests that HOX protein complexes may be both repressors and activators of transcription. Saleh et al. provide evidence for a mechanism for this dual function. The data suggest that complexes between HOX and PBC proteins recruit both histone deacetylases via the PBC partner and histone acetyltransferases (such as CBP) via the HOX partner. Furthermore, overexpression of the catalytic domain of protein kinase A (PKA) or the PKA target CBP stimulated HOX-PBX-mediated transcriptional activation. This implies that signals transduced through cyclic adenosine monophosphate may convert the HOX-PBX repressor into an activator through the activity of PKA, leading to the enhanced recruitment of the histone acetylase CBP to the HOX-PBX complex.

Saleh, M., Rambaldi, I., Yang, X.-J., and Featherstone, M.S. (2000) Cell signaling switches HOX-PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases. Mol. Cell. Biol. 20: 8623-8633. [Abstract] [Full Text]