视网膜母细胞瘤抗癌基因的点突变失活

Point mutational inactivation of the retinoblastoma antioncogene.

作者信息

Horowitz J M, Yandell D W, Park S H, Canning S, Whyte P, Buchkovich K, Harlow E, Weinberg R A, Dryja T P

机构信息

Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.

出版信息

Science. 1989 Feb 17;243(4893):937-40. doi: 10.1126/science.2521957.

DOI:10.1126/science.2521957

PMID:2521957

Abstract

The retinoblastoma (Rb) antioncogene encodes a nuclear phosphoprotein, p105-Rb, that forms protein complexes with the adenovirus E1A and SV40 large T oncoproteins. A novel, aberrant Rb protein detected in J82 bladder carcinoma cells was not able to form a complex with E1A and was less stable than p105-Rb. By means of a rapid method for the detection of mutations in Rb mRNA, this defective Rb protein was observed to result from a single point mutation within a splice acceptor sequence in J82 genomic DNA. This mutation eliminates a single exon and 35 amino acids from its encoded protein product.

摘要

视网膜母细胞瘤（Rb）抗癌基因编码一种核磷蛋白p105-Rb，它能与腺病毒E1A和SV40大T癌蛋白形成蛋白复合物。在J82膀胱癌细胞中检测到一种新型异常Rb蛋白，它无法与E1A形成复合物，且比p105-Rb更不稳定。通过一种快速检测Rb mRNA突变的方法，观察到这种有缺陷的Rb蛋白是由J82基因组DNA中剪接受体序列内的一个单点突变导致的。该突变从其编码的蛋白质产物中消除了一个外显子和35个氨基酸。