JunB can substitute for Jun in mouse development and cell proliferation.
The Jun and JunB components of the AP-1 transcription factor are known to have antagonistic functions. Here we show, by a knock-in strategy and a transgenic complementation approach, that Junb can substitute for absence of Jun during mouse development. Junb can rescue both liver and cardiac defects in Jun-null mice in a manner dependent on gene dosage. JunB restores the expression of genes regulated by Jun/Fos, but not those regulated by Jun/ATF, thereby rescuing Jun-dependent defects in vivo as well as in primary fibroblasts and fetal hepatoblasts in vitro. Thus, the transcriptionally less active JunB has the potential to substitute for Jun, indicating that the spatial and temporal regulation of expression of the transcription factor AP-1 may be more important than the coding sequence of its components.
Passegué
Emmanuelle
E
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Jochum
Wolfram
W
Behrens
Axel
A
Ricci
Romeo
R
Wagner
Erwin F
EF
D000818:Animals; D002455:Cell Division / Q000235:genetics* / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D016762:Genes, fos; D016758:Genes, jun; D006330:Heart Defects, Congenital / Q000235:genetics; D008099:Liver / Q000002:abnormalities; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1