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oai:ebiltegia.mondragon.edu:20.500.11984/145932026-06-19T06:15:49Zcom_20.500.11984_473com_20.500.11984_14090col_20.500.11984_477

00925njm 22002777a 4500 dc SUBRAMANIAM, Nanthakumar author Campion, Javier author RAFTER, Ingalill author OKRET, Sam author 2003 Glucocorticoid (GC) signalling influences the response of the cell to a number of other signals via a mechanism referred to as ‘cross-talk'. This cross-talk may act at several levels, including an interaction between the transcription factors involved in the signalling pathways. In the present paper, we demonstrate a novel functional interaction between GC and all-trans-retinoic acid (RA) signalling. We show that, in P19 embryonal carcinoma cells, GCs potentiate RA-induced expression of the murine Hoxb-1 gene through an autoregulatory element, b1-ARE, recognized by the Pbx1 and HOXB1 homoeodomain proteins. The synergistic effect of GC did not involve GC receptor (GR) binding to the b1-ARE, and the GC—GR complex alone was unable to activate transcription via the element. Furthermore, the ability of the GR to transactivate was not required, excluding expression of a GC-induced protein as the mechanism for the GC/RA synergy. Additional transfection experiments showed that the Pbx1/HOXB1 heterodimer was the target for the GC effect. Furthermore, functional dissection of the GR demonstrated that the DNA-binding domain (DBD) of the GR was required for the synergy. A physical interaction between the GR and Pbx1 proteins was demonstrated in vivo by co-immunoprecipitation experiments. These results are compatible with a model in which the GC/RA synergy is mediated by a direct interaction between the GR and Pbx1. On the basis of the ubiquitous expression of both GR and Pbx1, a number of genes regulated by Pbx are likely to be important targets for GC-mediated ‘cross-talk'. 1470-8728 0264-6021 https://hdl.handle.net/20.500.11984/14593 autoregulatory element HOXB1 P19 embryonal carcinoma cells protein–protein interaction Cross-talk between glucocorticoid and retinoic acid signals involving glucocorticoid receptor interaction with the homoeodomain protein Pbx1 Available to Purchase