Mao L, Merlo A, Bedi G, Shapiro G I, Edwards C D, Rollins B J, Sidransky D
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Cancer Res. 1995 Jul 15;55(14):2995-7.
p16INK4A and p15INK4B were initially identified as potent inhibitors of activated cyclin/cyclin-dependent kinase complexes. These genes were colocalized to chromosome 9p21, and p16 was subsequently found to be mutated in familial melanoma and deleted in a wide variety of sporadic cancers. We recently found that de novo methylation of a 5' CpG island led to transcriptional block of full-length p16 in many neoplasms. However, the presence of a truncated p16 transcript in methylated cell lines led us to investigate the presence of an alternative promoter or initiation site. We have now identified an abundant alternative p16 transcript in both methylated and unmethylated cell lines generated from a novel sequence (exon 1 beta) potentially involved in the complex regulation of these critical cell cycle genes.
p16INK4A和p15INK4B最初被鉴定为活化细胞周期蛋白/细胞周期蛋白依赖性激酶复合物的有效抑制剂。这些基因定位于9号染色体p21区域，随后发现p16在家族性黑色素瘤中发生突变，并在多种散发性癌症中缺失。我们最近发现，一个5'CpG岛的从头甲基化导致许多肿瘤中全长p16的转录受阻。然而，甲基化细胞系中存在截短的p16转录本，这促使我们研究是否存在替代启动子或起始位点。我们现已在甲基化和未甲基化细胞系中均鉴定出一种丰富的替代p16转录本，其源自一个可能参与这些关键细胞周期基因复杂调控的新序列（外显子1β）。
