Comparative analysis of the influence of the high-mobility group box 1 protein on DNA binding and transcriptional activation by the androgen, glucocorticoid, progesterone and mineralocorticoid receptors

Abstract

We performed a comparative analysis of the effect of high-mobility group box protein 1 (HMGB1) on DNA binding by the DNA-binding domains (DBDs) of the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. The affinity of the DBDs of the different receptors for the tyrosine aminotransferase glucocorticoid response element, a classical high-affinity binding element, was augmented up to 7-fold by HMGB1. We found no major differences in the effects of HMGB1 on DNA binding between the different steroid hormone receptors. In transient transfection assays, however, HMGB1 significantly enhances the activity of the glucocorticoid and progesterone receptors but not the androgen or mineralocorticoid receptor. We also investigated the effect of HMGB1 on the binding of the androgen receptor DBD to a subclass of directly repeated response elements that is recognized exclusively by the androgen receptor and not by the glucocorticoid, progesterone or mineralocorticoid receptor. Surprisingly, a deletion of 26 amino acid residues from the C-terminal extension of the androgen receptor DBD does not influence DNA binding but destroys its sensitivity to HMGB1. Deletion of the corresponding fragment in the DBDs of the glucocorticoid, progesterone and mineralocorticoid receptor destroyed their DNA binding. This 26-residue fragment is therefore essential for the influence of HMGB1 on DNA recognition by all steroid hormone receptors that were tested. However, it is dispensable for DNA binding by the androgen receptor.

Influence of nucleophosmin/B23 on DNA binding and transcriptional activity of the androgen receptor in prostate cancer cell

“…Nevertheless, it is interesting to notice that the presence of NPM did not affect the mobility of the complexes and that the use of an anti-NPM antibody did not result in the supershift of the retarded protein-DNA complex as would have been expected if NPM was present in the complex. Similar findings have already been reported for the highmobility group box 1 (HMGB1) protein which facilitates the DNA binding of several steroid receptors, including AR, without being present in the DNA/ receptor complex in EMSA experiments (Boonyaratanakornkit et al, 1998;Verrijdt et al, 2002). In a general hit-and-run mechanism, the authors have suggested that the HMGB1 protein might be a transient and unstable component of the steroid receptor/steroid response element complex that does not take part in the interactions within the final transcription activation complex.…”

Deleted in Breast Cancer 1, a Novel Androgen Receptor (AR) Coactivator That Promotes AR DNA-binding Activity

“…Among the short list of this type AR cofactors are HMG1/2 and nucleophosmin. HMG1/2 enhances DNA-binding activity of steroid hormone receptors such as progesterone receptor, glucocorticoid receptor, and AR (51,52). Nucleophosmin was shown to enhance AR DNA-binding and transcriptional activity (53).…”

Dual Function of an Amino-terminal Amphipatic Helix in Androgen Receptor-mediated Transactivation through Specific and Nonspecific Response Elements

“…10 and references therein). The reporter construct driven by the E1b promotor and containing two copies of the rat tyrosine aminotransferase-GRE was described previously (47). The thymidine kinase minimal promotor-driven reporter construct containing the slp and sc upstream enhancers and the C3 (1) intronic fragment as well as the pb promotor-driven construct have also been described (10).…”