title: Loss of the androgen receptor cofactor p44/WDR77 induces astrogliosis.
abstract: 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-κB activation. Silencing p21(Cip1) or NF-κB 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-κB signaling.
authors: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Bryce
authors: B
authors: Vincent
authors: Hong
authors: H
authors: Wu
authors: Shen
authors: S
authors: Gao
authors: Zhengxin
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000166:cytology / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D020868:Gene Silencing; D019426:Integrases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061213:Mortality, Premature; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000276:immunology*; D015854:Up-Regulation
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D010446:Peptide Fragments; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C503486:WDR77 protein, mouse; C045073:Cre recombinase; D019426:Integrases