Point mutations in v-Myb disrupt a cyclophilin-catalyzed negative regulatory mechanism.
Point mutations in v-Myb disrupt a cyclophilin-catalyzed negative regulatory mechanism.
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DOI：
10.1016/s1097-2765(00)80021-0
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发表时间：
1998
期刊：
影响因子：
16
通讯作者：
J. Leverson;Scott A. Ness
中科院分区：
文献类型：
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作者：
J. Leverson;Scott A. Ness
c-Myb蛋白受分子内相互作用控制，点突变可增强其致癌活性。我们测试了构象变化是否调节c-Myb，发现Cyp-40，一种广泛分布的亲环素和肽基脯氨酰异构酶，可以抑制c-Myb DNA结合活性。Cyp-40的抑制作用需要其C-末端蛋白相互作用结构域（与c-Myb特异性结合）和其N-末端催化结构域，并被竞争性抑制剂环孢菌素A阻断。Cyp-40不能结合或抑制致癌衍生物v-Myb，其具有突变的Cyp-40结合位点。这些结果表明，突变的v-Myb允许它逃避负调控机制介导的酶，如Cyp-40，并牵连肽基脯氨酰异构酶的转录，转化和分化的调节。
The c-Myb protein is controlled by intramolecular interactions, and point mutations can enhance its oncogenic activity. We tested whether conformational changes regulate c-Myb and found that Cyp-40, a widely distributed cyclophilin and peptidyl-prolyl isomerase, could inhibit c-Myb DNA binding activity. Inhibition by Cyp-40 required both its C-terminal protein-interaction domain, which bound specifically to c-Myb, and its N-terminal catalytic domain and was blocked by the competitive inhibitor cyclosporin A. Cyp-40 failed to bind or inhibit the oncogenic derivative v-Myb, which has a mutated Cyp-40 binding site. These results suggest that mutations in v-Myb allow it to evade a negative regulatory mechanism mediated by enzymes such as Cyp-40, and implicate peptidyl-prolyl isomerases in the regulation of transcription, transformation, and differentiation.