Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S5.

Մատենագիտական մանրամասներ
Հիմնական հեղինակներ: Frank, Christopher Lee, Ge, Xuecai, Xie, Zhigang, Zhou, Ying, Tsai, Li-Huei
Այլ հեղինակներ: Picower Institute for Learning and Memory
Ձևաչափ: Հոդված
Լեզու:en_US
Հրապարակվել է: 2011
Առցանց հասանելիություն:http://hdl.handle.net/1721.1/67329
https://orcid.org/0000-0003-1262-0592
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author Frank, Christopher Lee
Ge, Xuecai
Xie, Zhigang
Zhou, Ying
Tsai, Li-Huei
author2 Picower Institute for Learning and Memory
author_facet Picower Institute for Learning and Memory
Frank, Christopher Lee
Ge, Xuecai
Xie, Zhigang
Zhou, Ying
Tsai, Li-Huei
author_sort Frank, Christopher Lee
collection MIT
description The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S5.
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spelling mit-1721.1/673292022-09-30T01:22:36Z Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis Frank, Christopher Lee Ge, Xuecai Xie, Zhigang Zhou, Ying Tsai, Li-Huei Picower Institute for Learning and Memory Tsai, Li-Huei Frank, Christopher Lee Ge, Xuecai Xie, Zhigang Zhou, Ying Tsai, Li-Huei The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S5. Organogenesis 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. Rikagaku Kenkyūjo (Japan) Howard Hughes Medical Institute 2011-11-30T19:57:03Z 2011-11-30T19:57:03Z 2010-08 2010-07 Article http://purl.org/eprint/type/JournalArticle 0021-9258 1083-351X http://hdl.handle.net/1721.1/67329 Frank, C. L. et al. “Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis.” Journal of Biological Chemistry 285 (2010): 33324-33337. Web. 30 Nov. 2011. © 2011 by American Society for Biochemistry and Molecular Biology https://orcid.org/0000-0003-1262-0592 en_US http://dx.doi.org/10.1074/jbc.M110.140699 Journal of Biological Chemistry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf ASBMB
spellingShingle Frank, Christopher Lee
Ge, Xuecai
Xie, Zhigang
Zhou, Ying
Tsai, Li-Huei
Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis
title Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis
title_full Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis
title_fullStr Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis
title_full_unstemmed Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis
title_short Control of Activating Transcription Factor 4 (ATF4) Persistence by Multisite Phosphorylation Impacts Cell Cycle Progression and Neurogenesis
title_sort control of activating transcription factor 4 atf4 persistence by multisite phosphorylation impacts cell cycle progression and neurogenesis
url http://hdl.handle.net/1721.1/67329
https://orcid.org/0000-0003-1262-0592
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