Transformation by FosB requires a trans-activation domain missing in FosB2 that can be substituted by heterologous activation domains.
Transformation by FosB requires a trans-activation domain missing in FosB2 that can be substituted by heterologous activation domains.
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FosB 的转化需要 FosB2 中缺失的反式激活结构域，该结构域可以被异源激活结构域取代。
DOI：
10.1101/gad.6.4.667
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发表时间：
1992
影响因子：
10.5
通讯作者：
Verma,IM
中科院分区：
文献类型：
--
作者：
Wisdom,R;Yen,J;Rashid,D;Verma,IM
最近已经描述了通过选择性剪接从FosB基因衍生的两种功能不同的蛋白质。FosB蛋白有效地转化成纤维细胞，而FosB的羧基末端截短形式的FosB 2蛋白则不能，尽管这两种蛋白都可以作为与c-Jun蛋白的异二聚体复合物的一部分参与高亲和力的序列特异性DNA结合。我们在这里表明，这些蛋白质之间的功能差异是一个强大的富含脯氨酸的转录激活结构域的存在下，独特的FosB的羧基末端氨基酸的结果。这一结论得到了三条证据的支持：（1）FosB羧基末端区域的突变损害了转录激活，也降低了转化潜力，尽管事实上DNA作为与c-Jun的复合物的一部分的结合不受影响;（2）FosB特有的羧基末端区域在与GAL 4的DNA结合结构域融合时作为激活结构域发挥作用;和（3）通过融合几种不同的充分表征的反式激活结构域中的任何一种，可以赋予FosB 2转化潜力。这些结果确定了Fos蛋白转化的额外功能要求，并对AP-1转录复合物的促有丝分裂信号传导机制产生了影响。
Two functionally distinct proteins derived from the FosB gene by alternative splicing have recently been described. FosB protein transforms fibroblasts efficiently, whereas FosB2 protein, a carboxy-terminally truncated form of FosB, does not, despite the fact that both proteins can participate in high-affinity, sequence-specific DNA binding as part of a heterodimeric complex with c-Jun protein. We show here that the functional difference between these proteins is the result of the presence of a potent proline-rich transcriptional activation domain in the carboxy-terminal amino acids unique to FosB. This conclusion is supported by three lines of evidence: (1) Mutations in the carboxy-terminal region of FosB that impair transcriptional activation also reduce transforming potential, despite the fact that DNA binding as part of a complex with c-Jun is not affected; (2) the carboxy-terminal region unique to FosB functions as an activation domain when fused to the DNA-binding domain of GAL4; and (3) transforming potential can be conferred on FosB2 by fusing any of several different well-characterized trans-activation domains. These results identify an additional functional requirement for transformation by Fos proteins and have implications for the mechanism(s) of mitogenic signaling by the AP-1 transcription complex.