2026-06-25T19:53:23Zhttps://ebiltegia.mondragon.edu/oai/request

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

Cross-talk between glucocorticoid and retinoic acid signals involving glucocorticoid receptor interaction with the homoeodomain protein Pbx1 Available to Purchase SUBRAMANIAM, Nanthakumar Campion, Javier RAFTER, Ingalill OKRET, Sam autoregulatory element HOXB1 P19 embryonal carcinoma cells protein–protein interaction 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'. 2026-06-18T10:15:03Z 2026-06-18T10:15:03Z 2003 1470-8728 0264-6021 https://hdl.handle.net/20.500.11984/14593 eng © 2003 Biochemical Society Biochemical society