1. The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2
- Author
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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, and Hyunggee Kim
- Subjects
Receptors, Notch ,Neoplastic Stem Cells ,Oncogenes ,General Biochemistry, Genetics and Molecular Biology ,Signal Transduction ,Protein Binding - 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.
- Published
- 2022
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