Article ; Online: Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc.
Proceedings of the National Academy of Sciences of the United States of America
2024 Volume 121, Issue 18, Page(s) e2404188121
Abstract: ... implicated the Activator Protein-1 (AP-1) (Fos/Jun) transcription factor family members c-Fos and c-Jun ... that hepatocyte-restricted expression of a single chain c-Jun~Fra-2 protein, which functionally mimics the c-Jun ... Fra-2 AP-1 dimer, results in spontaneous HCC formation in c-Jun~Fra-2 ...
Abstract | Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. HCC incidence is on the rise, while treatment options remain limited. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies. While previous studies implicated the Activator Protein-1 (AP-1) (Fos/Jun) transcription factor family members c-Fos and c-Jun in HCC formation, the contribution of Fos-related antigens (Fra-) 1 and 2 is unknown. Here, we show that hepatocyte-restricted expression of a single chain c-Jun~Fra-2 protein, which functionally mimics the c-Jun/Fra-2 AP-1 dimer, results in spontaneous HCC formation in c-Jun~Fra-2 |
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MeSH term(s) | Animals ; Transcription Factor AP-1/metabolism ; Transcription Factor AP-1/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Mice ; Proto-Oncogene Proteins c-fos/metabolism ; Proto-Oncogene Proteins c-fos/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Proto-Oncogene Proteins c-jun/metabolism ; Fos-Related Antigen-2/metabolism ; Fos-Related Antigen-2/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Humans ; Hepatocytes/metabolism ; Protein Multimerization ; Gene Expression Regulation, Neoplastic ; Mice, Transgenic |
Chemical Substances | Transcription Factor AP-1 ; Proto-Oncogene Proteins c-myc ; Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-jun ; Fos-Related Antigen-2 ; fos-related antigen 1 ; Myc protein, mouse ; Fosl2 protein, mouse |
Language | English |
Publishing date | 2024-04-24 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
ZDB-ID | 209104-5 |
ISSN | 1091-6490 ; 0027-8424 |
ISSN (online) | 1091-6490 |
ISSN | 0027-8424 |
DOI | 10.1073/pnas.2404188121 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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