Dynamic in vivo interactions among Myc network members.
Dynamic in vivo interactions among Myc network members.
复制标题
Myc 网络成员之间的动态体内相互作用。
DOI：
10.1038/sj.onc.1204606
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发表时间：
2001
期刊：
影响因子：
8
通讯作者：
Prochownik,EV
中科院分区：
文献类型：
--
作者：
Yin,X;Landay,MF;Han,W;Levitan,ES;Watkins,SC;Levenson,RM;Farkas,DL;Prochownik,EV
Myc癌蛋白网络的成员（c-Myc、Max和Mad）在增殖、分化和凋亡中起重要作用。我们在成纤维细胞中表达了c-Myc、Max和三种Mad蛋白的嵌合绿色荧光蛋白（GFP）融合体。个别地，c-Myc和Mad蛋白定位于亚核斑点，而最大假设一个均匀的核图案。这些分布是共显性和动态的，但是，每个蛋白质假设其异源二聚体的合作伙伴的模式时，后者在更高的水平共表达。两个疯狂的成员，Mad 1和Mxi 1的缺失映射，表明负责核定位和斑点的域是可分离的。非斑点Mxi 1突变体作为转录抑制因子也不如野生型Mxi 1有效。c-Myc核斑点与参与mRNA加工的SC-35结构域不同。然而，在存在共表达Max的情况下，c-Myc而不是Mad共定位于SC-35基因座的子集。这些结果表明，Myc网络蛋白包含动态亚核结构，并且当与它们的正常异源二聚化伴侣共表达时表现为共显性。此外，c-Myc-Max异二聚体，而不是Max-Mad异二聚体，定位于活跃参与前mRNA转录/加工的病灶。这些发现表明Myc网络成员促进转录激活或抑制的新方法。
Members of the Myc oncoprotein network (c-Myc, Max, and Mad) play important roles in proliferation, differentiation, and apoptosis. We expressed chimeric green fluorescent protein (GFP) fusions of c-Myc, Max, and three Mad proteins in fibroblasts. Individually, c-Myc and Mad proteins localized in subnuclear speckles, whereas Max assumed a homogeneous nuclear pattern. These distributions were co-dominant and dynamic, however, as each protein assumed the pattern of its heterodimeric partner when the latter was co-expressed at a higher level. Deletion mapping of two Mad members, Mad1 and Mxi1, demonstrated that the domains responsible for nuclear localization and speckling are separable. A non-speckling Mxi1 mutant was also less effective as a transcriptional repressor than wild-type Mxi1. c-Myc nuclear speckles were distinct from SC-35 domains involved in mRNA processing. However, in the presence of co-expressed Max, c-Myc, but not Mad, co-localized to a subset of SC-35 loci. These results show that Myc network proteins comprise dynamic subnuclear structures and behave co-dominantly when co-expressed with their normal heterodimerization partners. In addition, c-Myc-Max heterodimers, but not Max-Mad heterodimers, localize to foci actively engaged in pre-mRNA transcription/processing. These findings suggest novel means by which Myc network members promote transcriptional activation or repression.