Yang A, Kaghad M, Wang Y, Gillett E, Fleming M D, Dötsch V, Andrews N C, Caput D, McKeon F
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell. 1998 Sep;2(3):305-16. doi: 10.1016/s1097-2765(00)80275-0.
We describe the cloning of p63, a gene at chromosome 3q27-29 that bears strong homology to the tumor suppressor p53 and to the related gene, p73. p63 was detected in a variety of human and mouse tissues, including proliferating basal cells of epithelial layers in the epidermis, cervix, urothelium, and prostate. Unlike p53, the p63 gene encodes multiple isotypes with remarkably divergent abilities to transactivate p53 reporter genes and induce apoptosis. Importantly, the predominant p63 isotypes in many epithelial tissues lack an acidic N terminus corresponding to the transactivation domain of p53. We demonstrate that these truncated p63 variants can act as dominant-negative agents toward transactivation by p53 and p63, and we suggest the possibility of physiological interactions among members of the p53 family.
我们描述了p63基因的克隆过程，该基因位于染色体3q27 - 29，与肿瘤抑制基因p53及相关基因p73具有高度同源性。在多种人类和小鼠组织中检测到了p63，包括表皮、子宫颈、尿路上皮和前列腺上皮层中增殖的基底细胞。与p53不同，p63基因编码多种亚型，这些亚型在反式激活p53报告基因和诱导细胞凋亡方面具有显著不同的能力。重要的是，许多上皮组织中主要的p63亚型缺乏与p53反式激活结构域相对应的酸性N末端。我们证明，这些截短的p63变体可作为p53和p63反式激活的显性负性因子，并且我们提出了p53家族成员之间存在生理相互作用的可能性。
