Funk M, Poensgen B, Graulich W, Jerome V, Müller R
Institut für Molekularbiologie und Tumorforschung, Phillips-Universität Marburg, Germany.
Mol Cell Biol. 1997 Feb;17(2):537-44. doi: 10.1128/MCB.17.2.537.
We have previously demonstrated that transformation by Fos is critically dependent on an intact DNA-binding domain (bZip) and a functional N-terminal transactivation motif (N-TM). We now show that a novel motif (C-terminal transactivation motif [C-TM]) near the C terminus also plays an important role in both transformation and the activation of AP1-dependent transcription and that the hydrophobic amino acids in the C-TM are functionally essential. The C-TM is the most crucial element in the C-terminal transactivation domain in Fos, as indicated by its relative strength and context-independent function. The C-TM is clearly different from the previously identified HOB2 domain, located N terminally to the C-TM, and the C-terminally positioned TATA-binding protein-binding domain. We also show that the C-terminal transactivation domain strongly synergizes with the HOB1-like N-TM, even when both domains are present on different proteins within a dimeric complex, and that the C-TM plays a crucial role in this cooperation. These observations can be corroborated in a model in which multiple contacts with the basal machinery are established either to stabilize the transcription complex or to facilitate its sequential assembly.
我们之前已经证明，Fos介导的转化严重依赖于完整的DNA结合结构域（bZip）和功能性的N端反式激活基序（N-TM）。我们现在表明，靠近C端的一个新基序（C端反式激活基序 [C-TM]）在转化和AP1依赖性转录激活中也发挥着重要作用，并且C-TM中的疏水氨基酸在功能上是必不可少的。C-TM是Fos中C端反式激活结构域中最关键的元件，这从其相对强度和与上下文无关的功能可以看出。C-TM明显不同于先前鉴定的位于C-TM N端的HOB2结构域以及位于C端的TATA结合蛋白结合结构域。我们还表明，即使两个结构域存在于二聚体复合物中的不同蛋白质上，C端反式激活结构域也能与HOB1样N-TM强烈协同作用，并且C-TM在这种协同作用中起关键作用。这些观察结果可以在一个模型中得到证实，在该模型中，与基础转录机制建立了多个接触点，以稳定转录复合物或促进其顺序组装。
