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 journalArticlepeer-review

6 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 languageEnglish
Article number111626
JournalCell Reports
Volume41
Issue number8
DOIs
Publication statusPublished - 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

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