Heterodimer formation of cJun and ATF-2 is responsible for induction of c-jun by the 243 amino acid adenovirus E1A protein.
The adenovirus E1A proteins differentially regulate AP-1-responsive genes. Collagenase and stromelysin are repressed by E1A, whereas the expression of c-jun is elevated. Inhibition of collagenase has been found to be exerted through the consensus AP-1 binding site TGAGTCA. Here we show that the distal AP-1 binding site in the c-jun promoter, the jun2TRE (TTACCTCA), is the decisive element of this promoter in mediating the positive response to the 243 amino acid E1A product. In vitro binding studies revealed that, in contrast to the consensus AP-1 site which is preferentially targeted by dimers composed of the Jun and Fos families, the jun2TRE binds heterodimers composed of cJun and ATF-2(-like) proteins. Since stimulation of c-jun transcription is a function of the transforming domain of E1A encoded by conserved region 1, cJun--ATF-2 may be one of the effector factors involved in transformation. The data further suggest that E1A can distinguish between cJun--cJun and cJun--ATF-2 in imposing opposite states of activity.
Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, University of Leiden, The Netherlands.
H
H
van Dam
M
M
Duyndam
R
R
Rottier
A
A
Bosch
L
L
de Vries-Smits
P
P
Herrlich
A
A
Zantema
P
P
Angel
A J
AJ
van der Eb
D016475:3T3 Cells; D051696:Activating Transcription Factors; D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D016758:Genes, jun; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D051696:Activating Transcription Factors; D017500:Adenovirus E1A Proteins; D001798:Blood Proteins; D009841:Oligonucleotides; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D000242:Cyclic AMP