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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gygi, Steven Bonni, Azad Villén, Judit Merlo, Paola Yuan, Zengqiang Lehtinen, Maria K. |
| Description | Author Affiliation: Yuan Z ( Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.) |
| Abstract | The protein kinase mammalian Sterile 20-like kinase 1 (MST1) plays a critical role in the regulation of cell death. Recent studies suggest that MST1 mediates oxidative stress-induced neuronal cell death by phosphorylating the transcription factor FOXO3 at serine 207, a site that is conserved in other FOXO family members. Here, we show that MST1-induced phosphorylation of FOXO1 at serine 212, corresponding to serine 207 in FOXO3, disrupts the association of FOXO1 with 14-3-3 proteins. Accordingly, MST1 mediates the nuclear translocation of FOXO1 in primary rat cerebellar granule neurons that are deprived of neuronal activity. We also find a requirement for MST1 in cell death of granule neurons upon withdrawal of growth factors and neuronal activity, and MST1 induces cell death in a FOXO1-dependent manner. Finally, we show that the MST1-regulatory, scaffold protein Nore1 is required for survival factor deprivation induced neuronal death. Collectively, these findings define MST1-FOXO1 signaling as an important link survival factor deprivation-induced neuronal cell death with implications for our understanding of brain development and neurological diseases. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 17 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-04-24 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Forkhead Transcription Factors Metabolism Gene Expression Regulation Hepatocyte Growth Factor Nerve Tissue Proteins Neurons Pathology Proto-Oncogene Proteins Animals Cell Death Cell Line Cerebellum Models, Biological Phosphorylation Signal Transduction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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