| First Author | Murphy SH | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 41 | Pages | 17117-22 |
| PubMed ID | 21949408 | Mgi Jnum | J:177464 |
| Mgi Id | MGI:5295133 | Doi | 10.1073/pnas.1114420108 |
| Citation | Murphy SH, et al. (2011) Tumor suppressor protein (p)53, is a regulator of NF-{kappa}B repression by the glucocorticoid receptor. Proc Natl Acad Sci U S A 108(41):17117-22 |
| abstractText | Glucocorticoids can inhibit inflammation by abrogating the activity of NF-kappaB, a family of transcription factors that regulates the production of proinflammatory cytokines. To understand the molecular mechanism of repression of NF-kappaB activity by glucocorticoids, we performed a high-throughput siRNA oligo screen to identify novel genes involved in this process. Here, we report that loss of p53, a tumor suppressor protein, impaired repression of NF-kappaB target gene transcription by glucocorticoids. Additionally, loss of p53 also impaired transcription of glucocorticoid receptor (GR) target genes, whereas upstream NF-kappaB and glucocorticoid receptor signaling cascades remained intact. We further demonstrate that p53 loss severely impaired glucocorticoid rescue of death in a mouse model of LPS shock. Our findings unveil a new role for p53 in the repression of NF-kappaB by glucocorticoids and suggest important implications for treatment of the proinflammatory microenvironments found in tumors with aberrant p53 activity. |
