Erratum: GADD34 induces cell death through inactivation of Akt following traumatic brain injury
| Autor: | Nilkantha Sen, Amany Tawfik, Sylvia B. Smith, Justin M. Farook, Shanu Markand, Krishnan M. Dhandapani, Darrell W. Brann, Jessica Shields, Tanusree Sen |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Apoptosis Disease Mice 0302 clinical medicine Protein Phosphatase 1 TBI Excitatory Amino Acid Agonists Homeostasis Phosphorylation Promoter Regions Genetic Cells Cultured Cerebral Cortex Neurons 0303 health sciences Endoplasmic Reticulum Stress Cell biology cell death GADD34 Original Article Corrigendum TRAF6 Protein Binding Transcriptional Activation Programmed cell death N-Methylaspartate Traumatic brain injury Primary Cell Culture Immunology Biology 03 medical and health sciences Cellular and Molecular Neuroscience Downregulation and upregulation medicine Animals Transcription factor Protein kinase B 030304 developmental biology TNF Receptor-Associated Factor 6 business.industry Akt ATF4 Ubiquitination Protein phosphatase 1 Cell Biology medicine.disease Activating Transcription Factor 4 Molecular biology Mice Inbred C57BL Brain Injuries Cancer research Reactive Oxygen Species business Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2013.336 |
| Popis: | Neuronal cell death contributes significantly to the pathology of traumatic brain injury (TBI) irrespective of the mode or severity of the injury. Activation of a pro-survival protein, Akt, is known to be regulated by an E3 ligase TRAF6 through a process of ubiquitination-coupled phosphorylation at its T308 residue. Here we show that upregulation of a pro-apototic protein, GADD34, attenuates TRAF6-mediated Akt activation in a controlled cortical impact model of TBI in mice. TBI induces the expression of GADD34 by stimulating binding of a stress inducible transcription factor, ATF4, to the GADD34 promoter. GADD34 then binds with TRAF6 and prevents its interaction with Akt. This event leads to retention of Akt in the cytosol and prevents phosphorylation at the T308 position. Finally, in vivo depletion of GADD34 using a lentiviral knockdown approach leads to a rescue of Akt activation and markedly attenuates TBI-induced cell death. |
| Databáze: | OpenAIRE |
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