| First Author | Bowe DB | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 22 | Pages | 8539-50 |
| PubMed ID | 16966374 | Mgi Jnum | J:115288 |
| Mgi Id | MGI:3691350 | Doi | 10.1128/MCB.01053-06 |
| Citation | Bowe DB, et al. (2006) O-GlcNAc integrates the proteasome and transcriptome to regulate nuclear hormone receptors. Mol Cell Biol 26(22):8539-50 |
| abstractText | Mechanisms controlling nuclear hormone receptors are a central question to mammalian developmental and disease processes. Herein, we show that a subtle increase in O-GlcNAc levels inhibits activation of nuclear hormone receptors. In vivo, increased levels of O-GlcNAc impair estrogen receptor activation and cause a decrease in mammary ductal side-branching morphogenesis associated with loss of progesterone receptors. Increased O-GlcNAc levels suppress transcriptional expression of coactivators and of the nuclear hormone receptors themselves. Surprisingly, increased O-GlcNAc levels are also associated with increased transcription of genes encoding corepressor proteins NCoR and SMRT. The association of the enzyme O-GlcNAc transferase with these corepressors contributes to specific regulation of nuclear hormone receptors by O-GlcNAc. Overall, transcriptional inhibition is related to the integrated effect of O-GlcNAc by direct modification of critical elements of the transcriptome and indirectly through O-GlcNAc modification of the proteasome. |
