An oncogenic mutation uncouples the v-Jun oncoprotein from positive regulation by the SAPK/JNK pathway in vivo

May, G. , Funk, M., Black, E.J., Clark, W., Hussain, S., Woodgett, J.R. and Gillespie, D.A.F. (1998) An oncogenic mutation uncouples the v-Jun oncoprotein from positive regulation by the SAPK/JNK pathway in vivo. Current Biology, 8(2), pp. 117-120. (doi: 10.1016/S0960-9822(98)70043-0) (PMID:9427647)

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Abstract

Stimulation of c-Jun transcriptional activity via phosphorylation mediated by the stress-activated or c-Jun amino-terminal (SAPK/JNK) subgroup of mitogen-activated protein kinases (MAP kinases) is thought to depend on a kinase-docking site (the delta region) within the amino-terminal activation domain, which is deleted from the oncogenic derivative, v-Jun [1] [2] [3]. This mutation markedly enhances v-Jun oncogenicity [4] [5]; however, its transcriptional consequences have not been resolved. In part, this reflects uncertainty as to whether binding of SAPK/JNK inhibits c-Jun function directly [6] [7] or, alternatively, serves to facilitate and maintain the specificity of positive regulatory phosphorylation [8]. Using a two-hybrid approach, we show that SAPK/JNK stimulates c-Jun transactivation in yeast and that this depends on both catalytic activity and physical interaction between the kinase and its substrate. Furthermore, c-Jun is active when tethered to DNA via SAPK/JNK, demonstrating that kinase binding does not preclude transactivation. Taken together, these results suggest that SAPK/JNK acts primarily as a positive regulator of c-Jun transactivation in situ, and that loss of the docking site physically uncouples v-Jun from this control. This loss-of-function model accounts for the deficit of v-Jun regulatory phosphorylation and repression of TPA response element (TRE)-dependent transcription observed in v-Jun-transformed cells and predicts that an important property of the oncoprotein is to antagonise SAPK/JNK-dependent gene expression.

Item Type:Articles (Letter)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:May, Dr Gerhard
Authors: May, G., Funk, M., Black, E.J., Clark, W., Hussain, S., Woodgett, J.R., and Gillespie, D.A.F.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
Q Science > QH Natural history > QH426 Genetics
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Current Biology
Publisher:Elsevier
ISSN:0960-9822
ISSN (Online):1879-0445

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