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dc.contributor.authorFrank, Christopher L.en_US
dc.contributor.authorGe, Xuecaien_US
dc.contributor.authorXie, Zhigangen_US
dc.contributor.authorZhou, Yingen_US
dc.contributor.authorTsai, Li-Hueien_US
dc.date.accessioned2012-01-11T22:29:46Z
dc.date.available2012-01-11T22:29:46Z
dc.date.issued2010-8-19en_US
dc.identifier.citationFrank, Christopher L., Xuecai Ge, Zhigang Xie, Ying Zhou, Li-Huei Tsai. "Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis*" Journal of Biological Chemistry 285(43): 33324-33337. (2010)en_US
dc.identifier.issn1083-351Xen_US
dc.identifier.urihttps://hdl.handle.net/2144/3306
dc.description.abstractOrganogenesis is a highly integrated process with a fundamental requirement for precise cell cycle control. Mechanistically, the cell cycle is composed of transitions and thresholds that are controlled by coordinated post-translational modifications. In this study, we describe a novel mechanism controlling the persistence of the transcription factor ATF4 by multisite phosphorylation. Proline-directed phosphorylation acted additively to regulate multiple aspects of ATF4 degradation. Stabilized ATF4 mutants exhibit decreased β-TrCP degron phosphorylation, β-TrCP interaction, and ubiquitination, as well as elicit early G1 arrest. Expression of stabilized ATF4 also had significant consequences in the developing neocortex. Mutant ATF4 expressing cells exhibited positioning and differentiation defects that were attributed to early G1 arrest, suggesting that neurogenesis is sensitive to ATF4 dosage. We propose that precise regulation of the ATF4 dosage impacts cell cycle control and impinges on neurogenesis.en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.rightsCopyright 2010 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.subjectCell cycleen_US
dc.subjectCell differentiationen_US
dc.subjectDevelopmenten_US
dc.subjectNeurodevelopmenten_US
dc.subjectNeuroprogenitor cellen_US
dc.subjectProtein phosphorylationen_US
dc.subjectProtein turnoveren_US
dc.subjectTranscription factorsen_US
dc.subjectUbiquitinationen_US
dc.titleControl of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis*en_US
dc.typeArticleen_US
dc.identifier.doi10.1074/jbc.M110.140699en_US
dc.identifier.pmid20724472en_US
dc.identifier.pmcid2963346en_US


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