Polyamine-modulated factor 1 (PMF-1) has been reported to interact with NF-E2 related factor 2 (Nrf-2) and activate the polyamine-induced transcription of spermidine/spermine N(1)-acetyltransferase (SSAT) gene. Polyamines are important regulators of cell growth and cell death and have been implicated in glucocorticoid-induced apoptosis. In the present study, we have identified and characterized new functional binding partners for PMF-1. Our results demonstrate that PMF-1 binds to the glucocorticoid receptor (GR). PMF-1 also represses glucocorticoid-induced transcription. Furthermore, we show that PMF-1 has an intrinsic repression activity, which could contribute to the repressive effect on GR. PMF-1 can also interact with the GR corepressor, receptor-interacting protein 140 (RIP140), but does not further enhance the repressive effect of RIP140. Our results suggest that PMF-1 has a broader function in regulation of genes and can contribute to glucocorticoid signaling.