B-Myb and cyclin D1 mediate heat shock element dependent activation of the human HSP70 promoter
B-Myb and cyclin D1 mediate heat shock element dependent activation of the human HSP70 promoter
复制标题
B-Myb 和细胞周期蛋白 D1 介导人 HSP70 启动子的热休克元件依赖性激活
作者：
H. Kamano;K. Klempnauer
先前的研究表明，作为Myb转录因子家族的保守成员，B-Myb是人类HSP70基因启动子的有效激活因子，但不激活含有Myb结合位点的启动子。我们现在更详细地研究了B-Myb的交换活化性质。我们在此报道B-Myb通过一种涉及热休克元件（HSE）的新机制激活HSP70启动子。对B-Myb的缺失分析表明，在B-Myb的中心有一个特定的结构域，而不是dna结合结构域，这是hse依赖的转激活所必需的。我们还表明，B-Myb的c端结构域的删除不影响hse依赖的转激活，但允许蛋白质激活含有Myb结合位点的启动子。这表明，在全长B-Myb的情况下，激活含有Myb结合位点启动子的能力受到抑制，并且HSE依赖和Myb结合位点依赖的转激活是B-Myb的不同功能。最后，我们报告了cyclin D1如B-Myb通过HSE强烈激活HSP70启动子。hse依赖的转激活是周期蛋白D1的一种新活性，似乎与Rb蛋白的磷酸化无关。我们的研究结果揭示了hse依赖基因激活与细胞周期G1/ s过渡期间表达的蛋白质之间有趣且意想不到的联系。
Previous studies have shown that B-Myb, a conserved member of the Myb transcription factor family, is a potent activator of the promoter of the human HSP70 gene but does not activate promoters containing Myb binding sites. We have now investigated the transactivation properties of B-Myb in more detail. We here report that B-Myb activates the HSP70 promoter by a novel mechanism which involves the heat shock element (HSE). Deletion analysis of B-Myb shows that a specific domain in the center of B-Myb, but not the DNA-binding domain is required for HSE-dependent transactivation. We also show that deletion of the C-terminal domain of B-Myb does not affect HSE-dependent transactivation but allows the protein to activate a promoter containing Myb binding sites. This suggests that the ability to activate Myb binding site containing promoters is repressed in the context of full length B-Myb and that HSE dependent and Myb binding site dependent transactivation are distinct functions of B-Myb. Finally, we report that cyclin D1 like B-Myb strongly activates the HSP70 promoter via the HSE. HSE-dependent transactivation is a novel activity of cyclin D1 and appears to be independent of the phosphorylation of the Rb protein. Our results reveal an interesting and unexpected connection between HSE-dependent gene activation and proteins expressed during the G1/S-transition of the cell cycle.