Amati B, Frank S R, Donjerkovic D, Taubert S
Department of Oncology, DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.
Biochim Biophys Acta. 2001 Mar 21;1471(3):M135-45. doi: 10.1016/s0304-419x(01)00020-8.
Deregulated expression of the c-myc proto-oncogene contributes to malignant progression of a variety of tumors. The c-Myc protein (or Myc) is a transcription factor that positively or negatively regulates expression of distinct sets of target genes. Transcriptional activation by Myc is mediated through dimerization with Max and binding to the DNA consensus sequence CA(C/T)GTG (the E-box). Transcriptional inhibition is mediated through distinct DNA elements, and may be due to functional interference with factors that transactivate via these sequences. We review here our current knowledge on these transcriptional activities of Myc and their relationship to its biological function. The findings that Myc interacts with subunits of histone acetyl-transferase (HAT) complexes and of the ATP-dependent chromatin remodeling complex, SWI/SNF, suggest that localized changes in chromatin structure may mediate Myc function. We present a working hypothesis for the concerted action of HAT and SWI/SNF complexes in Myc-activated transcription and argue that this model should prompt re-thinking of the experimental strategies and criteria used to identify Myc target genes.
c-myc原癌基因的表达失调促进了多种肿瘤的恶性进展。c-Myc蛋白（或Myc）是一种转录因子，可正向或负向调节不同组靶基因的表达。Myc介导的转录激活是通过与Max二聚化并结合DNA共有序列CA(C/T)GTG（E盒）来实现的。转录抑制是通过不同的DNA元件介导的，可能是由于对通过这些序列进行反式激活的因子产生功能干扰所致。我们在此综述了目前关于Myc这些转录活性及其与生物学功能关系的知识。Myc与组蛋白乙酰转移酶（HAT）复合物和ATP依赖的染色质重塑复合物SWI/SNF的亚基相互作用的发现表明，染色质结构的局部变化可能介导Myc的功能。我们提出了一个关于HAT和SWI/SNF复合物在Myc激活转录中协同作用的工作假说，并认为该模型应促使人们重新思考用于鉴定Myc靶基因的实验策略和标准。
