Mutations in the Jun delta region suggest an inverse correlation between transformation and transcriptional activation.
Mutations in the Jun delta region suggest an inverse correlation between transformation and transcriptional activation.
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DOI：
10.1073/pnas.89.2.618
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发表时间：
1992-01
影响因子：
11.1
通讯作者：
L. Håvarstein;I. Morgan;W. Y. Wong;P. Vogt
中科院分区：
文献类型：
--
作者：
L. Håvarstein;I. Morgan;W. Y. Wong;P. Vogt
病毒Jun蛋白（v-Jun）比其细胞对应物（c-Jun）更有效地转化鸡胚成纤维细胞（CEF）。在某些细胞类型中，v-Jun也是比c-Jun更强的转录激活因子。v-Jun和c-Jun之间的这些功能差异是由于v-Jun的缺失（称为“δ缺失”），这似乎削弱了Jun与负细胞调节分子的相互作用。这些观察结果表明，v-Jun的致瘤性可能是由于增强了激活靶基因转录的能力。为了验证这一假设，我们在鸡c-Jun的δ结构域中构建了几个缺失，并确定了它们的转化和反式激活特性。令人惊讶的是，我们发现突变体转化CEF和反式激活CEF中的胶原酶和transin启动子的能力之间存在负相关。相反，在F9鼠胚胎癌细胞中，c-Jun中的δ突变对反式激活没有显著影响。因此，δ区的功能是细胞类型特异性的。CEF中转化和反式激活之间的负相关性表明，v-Jun的强生长促进作用可能与未能激活生长衰减基因的转录有关。
The viral Jun protein (v-Jun) transforms chicken embryo fibroblasts (CEF) more effectively than its cellular counterpart (c-Jun). In certain cell types v-Jun is also a stronger transcriptional activator than c-Jun. These functional differences between v-Jun and c-Jun result from a deletion in v-Jun (referred to as "delta deletion") that seems to weaken the interaction of Jun with a negative cellular regulator molecule. These observations suggested that the oncogenicity of v-Jun may be due to an enhanced ability to activate transcription of target genes. To test this hypothesis, we constructed several deletions in the delta domain of chicken c-Jun and determined their transforming and transactivating properties. Surprisingly, we found an inverse correlation between the ability of the mutants to transform CEF and to transactivate the collagenase and transin promoters in CEF. In contrast, there was no significant effect of the delta mutations in c-Jun on transactivation in F9 murine embryonal carcinoma cells. The function of the delta region is therefore cell-type specific. The inverse correlation between transformation and transactivation in CEF suggests that the strong growth-promoting effect of v-Jun may be related to a failure to activate the transcription of growth attenuating genes.