Increased transforming activity of JunB and JunD by introduction of an heterologous homodimerization domain.
The closely-related proteins c-Jun, JunB and JunD form a family of transcription factors which require dimerization for DNA-binding and transcriptional activity. Dimerization is mediated by a conserved amphipathic alpha-helix located adjacent to a highly charged DNA-binding domain. The Jun proteins can form both homo- and heterodimers within the Jun family and can also cross-dimerize with the Fos proteins. When expressed at high levels in primary chicken cells, each mouse Jun displays distinct transforming capacities: c-Jun transforms efficiently, JunB transforms poorly, and JunD does not transform at all. The composition of the transforming dimers, however, is unknown. To study the activity of Jun-Jun homodimers we constructed artificial derivatives, denoted Juneb1, in which the naturally occurring dimerization domain has been replaced by an heterologous homodimerization domain from the Epstein-Barr virus transcription factor EB1. These derivatives were introduced into chicken cells and assayed for their ability to affect growth. Unexpectedly, all three Juneb1 proteins conferred a transformed phenotype to primary cultures, promoting sustained growth in low-serum medium and colony formation from single cells in agar. These data demonstrate that when forced to accumulate as homodimers, both JunB and JunD can transform cells. They also suggest that the poor transforming activity of JunB and the absence of transforming activity of JunD may be due to their inability to accumulate to high levels as homodimers.
Unité de Virologie Humaine, INSERM U 412, Ecole Normale Supérieure, Lyon, France.
L
L
Vandel
C M
CM
Pfarr
S
S
Huguier
L
L
Loiseau
A
A
Sergeant
M
M
Castellazzi
D000595:Amino Acid Sequence; D000818:Animals; D001704:Biopolymers / Q000502:physiology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002645:Chickens; D051379:Mice; D008969:Molecular Sequence Data; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry* / Q000502:physiology*; D011817:Rabbits; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000502:physiology
D001704:Biopolymers; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins