Heterodimerization with Fra-1 cooperates with the ERK pathway to stabilize c-Jun in response to the RAS oncoprotein

被引：0
作者：
F Talotta
T Mega
G Bossis
L Casalino
J Basbous
I Jariel-Encontre
M Piechaczyk
P Verde
机构：
[1] Institute of Genetics and Biophysics ‘A. Buzzati Traverso,
[2] ’ CNR,undefined
[3] Institut de Génétique Moléculaire de Montpellier,undefined
[4] CNRS,undefined
[5] Universités Montpellier I et II,undefined
[6] UMR 5535,undefined
[7] 3Current address: Department of Experimental and Clinical Medicine,undefined
[8] University of Catanzaro Magna Graecia,undefined
[9] Catanzaro,undefined
[10] Italy.,undefined
[11] 4Current address: Institut de Génétique Humaine,undefined
[12] Montpellier,undefined
[13] France.,undefined
来源：
Oncogene | 2010年 / 29卷
关键词：
c-Jun stability; FRA-1; heterodimerization; RAS transformation;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Multiple tumorigenic pathways converge on the activating protein-1 (AP-1) family of dimeric transcription complexes by affecting transcription, mRNA decay, posttranslational modifications, as well as stability of its JUN and FOS components. Several mechanisms have been implicated in the phosphorylation- and ubiquitylation-dependent control of c-Jun protein stability. Although its dimer composition has a major role in the regulation of AP-1, little is known about the influence of heterodimerization partners on the half-life of c-Jun. The FOS family member Fra-1 is overexpressed in various tumors and cancer cell lines wherein it controls motility, invasiveness, cell survival and cell division. Oncogene-induced accumulation of Fra-1 results from both increased transcription and phosphorylation-dependent stabilization of the protein. In this report, we describe a novel role of Fra-1 as a posttranslational regulator of c-Jun. By using both constitutively and inducible transformed rat thyroid cell lines, we found that c-Jun is stabilized in response to RAS oncoprotein expression. This stabilization requires the activity of the extracellular signal-related kinase (ERK) pathway, along with c-Jun heterodimerization with Fra-1. In particular, heterodimerization with Fra-1 inhibits c-Jun breakdown by a mechanism dependent on the phosphorylation of the Fra-1 C-terminal domain that positively controls the stability of the protein in response to ERK signaling. Therefore, Fra-1 modulates AP-1 dimer composition by promoting the accumulation of c-Jun in response to oncogenic RAS signaling.
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页码：4732 / 4740
页数：8
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