Dang C V
Department of Medicine, Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Biochim Biophys Acta. 1991 Dec 10;1072(2-3):103-13. doi: 10.1016/0304-419x(91)90009-a.
Genetic alterations of the c-myc locus in various malignancies and the ability of c-myc to transform cultured cells and induce tumors in transgenic animals attest to its central role in many neoplasms. By dissecting the c-Myc protein, a number of critical functional domains of c-Myc have been identified and characterized; these findings suggest a model for c-Myc function and intracellular activity (Fig. 4). c-Myc is synthesized in the cytoplasm and undergoes oligomerization another protein such as Max. Its nuclear localization signal allows c-Myc to be targeted to and retained in the nucleus, where the protein seeks out and binds to specific DNA sites, perhaps facilitated by c-Myc's ability to bind non-specifically to DNA. Once bound to specific DNA sequences, c-Myc then activates or inhibits transcription of a number of target genes, with consequent alterations in cell growth and differentiation. Continued studies of c-Myc and its partner Max should further elucidate the mechanisms by which c-Myc can contribute both to the regulation of normal cell growth and the alteration in that regulation in neoplasia.
c-myc基因座在各种恶性肿瘤中的遗传改变，以及c-myc在体外转化细胞和在转基因动物中诱导肿瘤的能力，证明了其在许多肿瘤中的核心作用。通过剖析c-Myc蛋白，已鉴定并表征了c-Myc的多个关键功能域；这些发现提示了一个c-Myc功能和细胞内活性的模型（图4）。c-Myc在细胞质中合成，并与另一种蛋白质如Max发生寡聚化。其核定位信号使c-Myc靶向并保留在细胞核中，在细胞核中该蛋白质寻找并结合到特定的DNA位点，这可能得益于c-Myc与DNA非特异性结合的能力。一旦与特定的DNA序列结合，c-Myc随后激活或抑制许多靶基因的转录，从而导致细胞生长和分化的改变。对c-Myc及其伙伴Max的持续研究应能进一步阐明c-Myc既能促进正常细胞生长调节又能导致肿瘤中该调节改变的机制。
