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AP-1 in mouse development and tumorigenesis
W Jochum1, E Passegué, E F Wagner
1Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Abstract:
Genetically modified mice have provided important insights into the biological functions of the dimeric transcription factor complex AP-1. Extensive analyses of mice and cells with genetically modified Fos or Jun proteins provide novel insights into the physiological functions of AP-1 proteins. Using knock-out strategies it was found that some components, such as c-Fos, FosB and JunD are dispensable, whereas others, like c-Jun, JunB and Fra-1 are essential in embryonic development and/or in the adult organism. Besides the specific roles of AP-1 proteins in developmental processes, we are beginning to obtain a better molecular understanding of the cell-context dependent function of AP-1 in cell proliferation and apoptosis, in bone biology as well as in multistep tumorigenesis.
Insights
Genetically modified mice reveal the essential roles of Activator Protein-1 (AP-1) components like c-Jun. Some AP-1 proteins are dispensable, while others are crucial for development and adult life.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- The dimeric transcription factor complex Activator Protein-1 (AP-1) regulates gene expression.
- Understanding AP-1's biological functions is crucial for various physiological processes.
Purpose of the Study:
- To investigate the physiological roles of AP-1 proteins using genetically modified mice.
- To elucidate the essentiality of specific Fos and Jun family members in development and adult life.
Main Methods:
- Generation and analysis of genetically modified mice (knock-out strategies).
- Extensive analyses of mice and cells with modified Fos or Jun proteins.
Main Results:
- Identified c-Fos, FosB, and JunD as dispensable AP-1 components.
- Demonstrated that c-Jun, JunB, and Fra-1 are essential for embryonic development and/or adult organisms.
- Gained insights into AP-1's context-dependent roles in cell proliferation, apoptosis, bone biology, and tumorigenesis.
Conclusions:
- Specific AP-1 proteins have distinct and essential roles in organismal development and homeostasis.
- AP-1's function is highly dependent on cellular context, influencing critical processes like proliferation, apoptosis, and cancer development.