| First Author | Vincent B | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 17 | Pages | 3500-12 |
| PubMed ID | 22751923 | Mgi Jnum | J:196527 |
| Mgi Id | MGI:5488689 | Doi | 10.1128/MCB.00298-12 |
| Citation | Vincent B, et al. (2012) Loss of the androgen receptor cofactor p44/WDR77 induces astrogliosis. Mol Cell Biol 32(17):3500-12 |
| abstractText | Astrogliosis is induced by neuronal damage and is also a pathological feature of the major aging-related neurodegenerative disorders. The mechanisms that control the cascade of astrogliosis have not been well established. In a previous study, we identified a novel androgen receptor (AR)-interacting protein, p44/WDR77, that plays a critical role in the proliferation and differentiation of prostate epithelial cells. In the present study, we found that deletion of the p44/WDR77 gene caused premature death with dramatic astrogliosis in mouse brain. We further found that p44/WDR77 is expressed in astrocytes and that loss of p44/WDR77 expression in astrocytes leads to growth arrest and astrogliosis. The astrocyte activation induced by deletion of the p44/WDR77 gene was associated with upregulation of p21(Cip1) expression and NF-kappaB activation. Silencing p21(Cip1) or NF-kappaB p65 expression with short hairpin RNA (shRNA) abolished astrocyte activation and rescued the astrocyte growth inhibition induced by deletion of the p44/WDR77 gene. Our results reveal a novel role for p44/WDR77 in the control of astrocyte activation through p21(Cip1) and NF-kappaB signaling. |
