HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation

Ka Lung Cheung; Anbalagan Jaganathan; Yuan Hu; Feihong Xu; Alannah Lejeune; Rajal Sharma; Cristina I. Caescu; Jamel Meslamani; Adam Vincek; Fan Zhang; Kyung Lee; Nilesh Zaware; Amina Abdul Qayum; Chunyan Ren; Mark H. Kaplan; John Cijiang He; Huabao Xiong; Ming Ming Zhou

doi:10.1073/pnas.2117112119

HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation

Ka Lung Cheung, Anbalagan Jaganathan, Yuan Hu, Feihong Xu, Alannah Lejeune, Rajal Sharma, Cristina I. Caescu, Jamel Meslamani, Adam Vincek, Fan Zhang, Kyung Lee, Nilesh Zaware, Amina Abdul Qayum, Chunyan Ren, Mark H. Kaplan, John Cijiang He, Huabao Xiong, Ming Ming Zhou

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1 Scopus citations

Abstract

SignificanceSTAT3 (signal transducer and activator of transcription 3) is a master transcription factor that organizes cellular responses to cytokines and growth factors and is implicated in inflammatory disorders. STAT3 is a well-recognized therapeutic target for human cancer and inflammatory disorders, but how its function is regulated in a cell type-specific manner has been a major outstanding question. We discovered that Stat3 imposes self-directed regulation through controlling transcription of its own regulator homeodomain-interacting protein kinase 2 (Hipk2) in a T helper 17 (Th17) cell-specific manner. Our validation of the functional importance of the Stat3-Hipk2 axis in Th17 cell development in the pathogenesis of T cell-induced colitis in mice suggests an approach to therapeutically treat inflammatory bowel diseases that currently lack a safe and effective therapy.

Original language	English
Pages (from-to)	e2117112119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	14
DOIs	https://doi.org/10.1073/pnas.2117112119
State	Published - 5 Apr 2022

Keywords

STAT3
Th17 cell differentiation
chromatin biology
gene transcription

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10.1073/pnas.2117112119

Cite this

Cheung, K. L., Jaganathan, A., Hu, Y., Xu, F., Lejeune, A., Sharma, R., Caescu, C. I., Meslamani, J., Vincek, A., Zhang, F., Lee, K., Zaware, N., Qayum, A. A., Ren, C., Kaplan, M. H., He, J. C., Xiong, H., & Zhou, M. M. (2022). HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation. Proceedings of the National Academy of Sciences of the United States of America, 119(14), e2117112119. https://doi.org/10.1073/pnas.2117112119

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title = "HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation",

abstract = "SignificanceSTAT3 (signal transducer and activator of transcription 3) is a master transcription factor that organizes cellular responses to cytokines and growth factors and is implicated in inflammatory disorders. STAT3 is a well-recognized therapeutic target for human cancer and inflammatory disorders, but how its function is regulated in a cell type-specific manner has been a major outstanding question. We discovered that Stat3 imposes self-directed regulation through controlling transcription of its own regulator homeodomain-interacting protein kinase 2 (Hipk2) in a T helper 17 (Th17) cell-specific manner. Our validation of the functional importance of the Stat3-Hipk2 axis in Th17 cell development in the pathogenesis of T cell-induced colitis in mice suggests an approach to therapeutically treat inflammatory bowel diseases that currently lack a safe and effective therapy.",

keywords = "STAT3, Th17 cell differentiation, chromatin biology, gene transcription",

author = "Cheung, {Ka Lung} and Anbalagan Jaganathan and Yuan Hu and Feihong Xu and Alannah Lejeune and Rajal Sharma and Caescu, {Cristina I.} and Jamel Meslamani and Adam Vincek and Fan Zhang and Kyung Lee and Nilesh Zaware and Qayum, {Amina Abdul} and Chunyan Ren and Kaplan, {Mark H.} and He, {John Cijiang} and Huabao Xiong and Zhou, {Ming Ming}",

year = "2022",

month = apr,

day = "5",

doi = "10.1073/pnas.2117112119",

language = "English",

volume = "119",

pages = "e2117112119",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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publisher = "National Academy of Sciences",

number = "14",

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Cheung, KL, Jaganathan, A, Hu, Y, Xu, F, Lejeune, A, Sharma, R, Caescu, CI, Meslamani, J, Vincek, A, Zhang, F, Lee, K, Zaware, N, Qayum, AA, Ren, C, Kaplan, MH, He, JC, Xiong, H & Zhou, MM 2022, 'HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 14, pp. e2117112119. https://doi.org/10.1073/pnas.2117112119

TY - JOUR

T1 - HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation

AU - Cheung, Ka Lung

AU - Jaganathan, Anbalagan

AU - Hu, Yuan

AU - Xu, Feihong

AU - Lejeune, Alannah

AU - Sharma, Rajal

AU - Caescu, Cristina I.

AU - Meslamani, Jamel

AU - Vincek, Adam

AU - Zhang, Fan

AU - Lee, Kyung

AU - Zaware, Nilesh

AU - Qayum, Amina Abdul

AU - Ren, Chunyan

AU - Kaplan, Mark H.

AU - He, John Cijiang

AU - Xiong, Huabao

AU - Zhou, Ming Ming

PY - 2022/4/5

Y1 - 2022/4/5

N2 - SignificanceSTAT3 (signal transducer and activator of transcription 3) is a master transcription factor that organizes cellular responses to cytokines and growth factors and is implicated in inflammatory disorders. STAT3 is a well-recognized therapeutic target for human cancer and inflammatory disorders, but how its function is regulated in a cell type-specific manner has been a major outstanding question. We discovered that Stat3 imposes self-directed regulation through controlling transcription of its own regulator homeodomain-interacting protein kinase 2 (Hipk2) in a T helper 17 (Th17) cell-specific manner. Our validation of the functional importance of the Stat3-Hipk2 axis in Th17 cell development in the pathogenesis of T cell-induced colitis in mice suggests an approach to therapeutically treat inflammatory bowel diseases that currently lack a safe and effective therapy.

AB - SignificanceSTAT3 (signal transducer and activator of transcription 3) is a master transcription factor that organizes cellular responses to cytokines and growth factors and is implicated in inflammatory disorders. STAT3 is a well-recognized therapeutic target for human cancer and inflammatory disorders, but how its function is regulated in a cell type-specific manner has been a major outstanding question. We discovered that Stat3 imposes self-directed regulation through controlling transcription of its own regulator homeodomain-interacting protein kinase 2 (Hipk2) in a T helper 17 (Th17) cell-specific manner. Our validation of the functional importance of the Stat3-Hipk2 axis in Th17 cell development in the pathogenesis of T cell-induced colitis in mice suggests an approach to therapeutically treat inflammatory bowel diseases that currently lack a safe and effective therapy.

KW - STAT3

KW - Th17 cell differentiation

KW - chromatin biology

KW - gene transcription

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U2 - 10.1073/pnas.2117112119

DO - 10.1073/pnas.2117112119

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AN - SCOPUS:85127298845

VL - 119

SP - e2117112119

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -

HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation

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