The cell-type-specific activator region of c-Jun juxtaposes constitutive and negatively regulated domains.
Dissection of the cell-type-specific activation region in c-Jun reveals two functionally separable regulatory subdomains. One subdomain (a1) functions as a transcriptional activator; adjacent to it is a newly identified domain (epsilon) which, together with the previously defined delta region, interacts with a cellular factor that modulates the action of a1. Mutants that lack epsilon are constitutively active and do not interact with the cell-type-specific repressor, whereas mutants that have sustained changes in a1 exhibit a reduced trans-activation potential but retain the ability to interact with the repressor. This bipartite and modular organization of the a1/epsilon domain is further established by demonstrating that a1 can be replaced by the heterologous acidic activator of VP16 and retain proper negative regulation by the cell-specific c-Jun inhibitor along with epsilon and delta. Repression of Jun activity by the inhibitor is not caused by a change in stability, nuclear localization, or DNA-binding activity of the protein. Instead the inhibitor apparently regulates transcriptional activation by interacting directly with delta/epsilon and perhaps masking the a1 domain. These studies suggest that multifunctional activation domains, which are structurally complex, may play an important role in the mechanisms that govern inducible tissue-specific gene expression.
Baichwal
V R
VR
Howard Hughes Medical Institute, University of California, Berkeley 94720.
Park
A
A
Tjian
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins