The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2

Eun Jung Kim; Jung Yun Kim; Sung Ok Kim; Nayoung Hong; Sang Hun Choi; Min Gi Park; Junseok Jang; Seok Won Ham; Sunyoung Seo; Seon Yong Lee; Kanghun Lee; Hyeon Ju Jeong; Sung Jin Kim; Sohee Jeong; Kyungim Min; Sung Chan Kim; Xiong Jin; Se Hoon Kim; Sung Hak Kim; Hyunggee Kim

doi:10.1016/j.celrep.2022.111626

The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2

Eun Jung Kim, Jung Yun Kim, Sung Ok Kim, Nayoung Hong, Sang Hun Choi, Min Gi Park, Junseok Jang, Seok Won Ham, Sunyoung Seo, Seon Yong Lee, Kanghun Lee, Hyeon Ju Jeong, Sung Jin Kim, Sohee Jeong, Kyungim Min, Sung Chan Kim, Xiong Jin, Se Hoon Kim, Sung Hak Kim, Hyunggee Kim

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

Original language	English
Article number	111626
Journal	Cell Reports
Volume	41
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2022.111626
Publication status	Published - 2022 Nov 22

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Keywords

CP: Cancer
DDX17
JAG1
JICD1
JICD1 transcriptional complex
SMAD3
TGIF2
glioblastoma

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2022.111626

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Kim, E. J., Kim, J. Y., Kim, S. O., Hong, N., Choi, S. H., Park, M. G., Jang, J., Ham, S. W., Seo, S., Lee, S. Y., Lee, K., Jeong, H. J., Kim, S. J., Jeong, S., Min, K., Kim, S. C., Jin, X., Kim, S. H., Kim, S. H., & Kim, H. (2022). The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2. Cell Reports, 41(8), Article 111626. https://doi.org/10.1016/j.celrep.2022.111626

Kim, EJ, Kim, JY, Kim, SO, Hong, N, Choi, SH, Park, MG, Jang, J, Ham, SW, Seo, S, Lee, SY, Lee, K, Jeong, HJ, Kim, SJ, Jeong, S, Min, K, Kim, SC, Jin, X, Kim, SH, Kim, SH & Kim, H 2022, 'The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2', Cell Reports, vol. 41, no. 8, 111626. https://doi.org/10.1016/j.celrep.2022.111626

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abstract = "Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.",

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AU - Kim, Eun Jung

AU - Kim, Jung Yun

AU - Kim, Sung Ok

AU - Hong, Nayoung

AU - Choi, Sang Hun

AU - Park, Min Gi

AU - Jang, Junseok

AU - Ham, Seok Won

AU - Seo, Sunyoung

AU - Lee, Seon Yong

AU - Lee, Kanghun

AU - Jeong, Hyeon Ju

AU - Kim, Sung Jin

AU - Jeong, Sohee

AU - Min, Kyungim

AU - Kim, Sung Chan

AU - Jin, Xiong

AU - Kim, Se Hoon

AU - Kim, Sung Hak

AU - Kim, Hyunggee

PY - 2022/11/22

Y1 - 2022/11/22

N2 - Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

AB - Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

KW - CP: Cancer

KW - DDX17

KW - JAG1

KW - JICD1

KW - JICD1 transcriptional complex

KW - SMAD3

KW - TGIF2

KW - glioblastoma

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DO - 10.1016/j.celrep.2022.111626

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SN - 2211-1247

VL - 41

JO - Cell Reports

JF - Cell Reports

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ER -

The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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