JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production

c-Jun N-terminal kinases (JNKs) regulate cell proliferation and differentiation via phosphorylating such transcription factors as c-Jun. The function of JNKs in retinogenesis remains to be elucidated. Here, we report that knocking out <i>Jnk1</i>, but not <i>Jnk2</i>, increas...

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Main Authors: Mingyu Pan, Haiyang Hu, Rui Wang, Yi Zhou, Lele Zhang, Chen Wang, Quanyi Wang
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/9/970
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spelling doaj-af9acaaf670d4115b7ab83919bc461d32020-11-25T01:02:57ZengMDPI AGCells2073-44092019-08-018997010.3390/cells8090970cells8090970JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor ProductionMingyu Pan0Haiyang Hu1Rui Wang2Yi Zhou3Lele Zhang4Chen Wang5Quanyi Wang6State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Chinac-Jun N-terminal kinases (JNKs) regulate cell proliferation and differentiation via phosphorylating such transcription factors as c-Jun. The function of JNKs in retinogenesis remains to be elucidated. Here, we report that knocking out <i>Jnk1</i>, but not <i>Jnk2</i>, increased the number of photoreceptors, thus enhancing the electroretinogram (ERG) responses. Intriguingly, Notch1, a well-established negative regulator of photoreceptor genesis, was significantly attenuated in <i>Jnk1</i> knockout (KO) mice compared to wild-type mice. Mechanistically, light specifically activated JNK1 to phosphorylate c-Jun, which in turn induced Notch1 transcription. The identified JNK1&#8722;c-Jun&#8722;Notch1 axis strongly inhibited photoreceptor-related transcriptional factor expression and ultimately impaired photoreceptor opsin expression. Our study uncovered an essential function of JNK1 in retinogenesis, revealing JNK1 as a potential candidate for targeting ophthalmic diseases.https://www.mdpi.com/2073-4409/8/9/970JNK1c-JunNotch1opsinphotoreceptorretinavision
collection DOAJ
language English
format Article
sources DOAJ
author Mingyu Pan
Haiyang Hu
Rui Wang
Yi Zhou
Lele Zhang
Chen Wang
Quanyi Wang
spellingShingle Mingyu Pan
Haiyang Hu
Rui Wang
Yi Zhou
Lele Zhang
Chen Wang
Quanyi Wang
JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production
Cells
JNK1
c-Jun
Notch1
opsin
photoreceptor
retina
vision
author_facet Mingyu Pan
Haiyang Hu
Rui Wang
Yi Zhou
Lele Zhang
Chen Wang
Quanyi Wang
author_sort Mingyu Pan
title JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production
title_short JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production
title_full JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production
title_fullStr JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production
title_full_unstemmed JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production
title_sort jnk1 induces notch1 expression to regulate genes governing photoreceptor production
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2019-08-01
description c-Jun N-terminal kinases (JNKs) regulate cell proliferation and differentiation via phosphorylating such transcription factors as c-Jun. The function of JNKs in retinogenesis remains to be elucidated. Here, we report that knocking out <i>Jnk1</i>, but not <i>Jnk2</i>, increased the number of photoreceptors, thus enhancing the electroretinogram (ERG) responses. Intriguingly, Notch1, a well-established negative regulator of photoreceptor genesis, was significantly attenuated in <i>Jnk1</i> knockout (KO) mice compared to wild-type mice. Mechanistically, light specifically activated JNK1 to phosphorylate c-Jun, which in turn induced Notch1 transcription. The identified JNK1&#8722;c-Jun&#8722;Notch1 axis strongly inhibited photoreceptor-related transcriptional factor expression and ultimately impaired photoreceptor opsin expression. Our study uncovered an essential function of JNK1 in retinogenesis, revealing JNK1 as a potential candidate for targeting ophthalmic diseases.
topic JNK1
c-Jun
Notch1
opsin
photoreceptor
retina
vision
url https://www.mdpi.com/2073-4409/8/9/970
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AT yizhou jnk1inducesnotch1expressiontoregulategenesgoverningphotoreceptorproduction
AT lelezhang jnk1inducesnotch1expressiontoregulategenesgoverningphotoreceptorproduction
AT chenwang jnk1inducesnotch1expressiontoregulategenesgoverningphotoreceptorproduction
AT quanyiwang jnk1inducesnotch1expressiontoregulategenesgoverningphotoreceptorproduction
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