Transcriptional activation by the v-Jun oncoprotein is independent of positive regulatory phosphorylation.
Growth factors, phorbol esters, and oncogenes such as ras, src, and sis are believed to stimulate c-Jun transcriptional activation by inducing increased phosphorylation at two serine residues (S63 and S73) within the N-terminal transactivation domain. Although S63 and S73 are conserved in the mutant v-Jun oncoprotein, they are not phosphorylated by two enzymes which target the corresponding residues in c-Jun in vitro; namely a partially purified c-Jun kinase from TPA-stimulated U937 cells and purified p54 mitogen activated protein (MAP) kinase. In addition, v-Jun activates transcription more strongly than c-Jun when fused to the Gal4 DNA-binding domain, and transcriptional activation by Gal4-v-Jun is unaffected when S63, S73, or both, are replaced with non-phosphorylatable alanine residues, amino acid substitutions which severely impair transcriptional activation by Gal4-c-Jun. The novel biochemical and transcriptional properties of v-Jun result from deletion of a 27 amino acid segment, termed delta, which is important for transforming activity. On the basis of these results we propose that unlike c-Jun, v-Jun transcriptional activation is independent of positive regulatory phosphorylation and that this may contribute to oncogenesis by v-Jun.
Cancer Research Campaign Beatson Laboratories, Beatson Institute for Cancer Research, Glasgow, UK.
E J
EJ
Black
A D
AD
Catling
J R
JR
Woodgett
A
A
Kilbey
D A
DA
Gillespie
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002642:Chick Embryo; D006801:Humans; D016759:Oncogene Protein p65(gag-jun) / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D016759:Oncogene Protein p65(gag-jun); D016755:Proto-Oncogene Proteins c-jun; D017871:Calcium-Calmodulin-Dependent Protein Kinases