Wang Q, Zhang H, Kajino K, Greene M I
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Oncogene. 1998 Oct 15;17(15):1939-48. doi: 10.1038/sj.onc.1202403.
c-Myc, a proto-oncogene that is implicated in tumorigenesis, embryonic development and apoptosis, can physically associate with BRCA1. We have found that BRCA1 interacts with c-Myc in yeast, in in vitro assays and in mammalian cells. Endogenous interactions between BRCA1 and c-Myc were also observed. Efficient BRCA1-Myc association requires the intact helix-loop-helix region of c-Myc, a motif involved in Myc-Max dimerization. BRCA1 does not however bind to Max. Our studies revealed that BRCA1 represses Myc-mediated transcription while having no effect on some other transcriptional activities. Furthermore, BRCA1 reverses the phenotype of embryonic fibroblasts transformed by the activation of Myc and Ras, but only minimally affects the transformed phenotype induced by SV40 virus. These data indicate that BRCA1 may function as a tumor suppressor by regulating the behavior of c-Myc and provide a molecular explanation for some of the effects of the BRCA1 gene product.
c-Myc是一种原癌基因，与肿瘤发生、胚胎发育和细胞凋亡有关，它能与BRCA1直接发生相互作用。我们发现在酵母、体外试验以及哺乳动物细胞中，BRCA1与c-Myc存在相互作用。同时也观察到BRCA1和c-Myc之间存在内源性相互作用。BRCA1与Myc的有效结合需要c-Myc完整的螺旋-环-螺旋区域，该基序参与Myc-Max二聚化。然而，BRCA1并不与Max结合。我们的研究表明，BRCA1可抑制Myc介导的转录，而对其他一些转录活性没有影响。此外，BRCA1可逆转因Myc和Ras激活而转化的胚胎成纤维细胞的表型，但对SV40病毒诱导的转化表型影响极小。这些数据表明，BRCA1可能通过调节c-Myc的行为发挥肿瘤抑制作用，并为BRCA1基因产物的某些作用提供了分子解释。
