Gilmore T D, Temin H M
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
J Virol. 1988 Mar;62(3):703-14. doi: 10.1128/JVI.62.3.703-714.1988.
The transforming protein encoded by the v-rel oncogene of the highly oncogenic avian retrovirus reticuloendotheliosis virus strain T (Rev-T) is a 59,000-dalton protein, p59v-rel. The mechanism by which p59v-rel induces transformation of early lymphoid cells is unknown. As a step towards understanding the mechanism of v-rel-induced transformation, we sought to establish the subcellular site of action of p59v-rel. In this report, we show that p59v-rel contains sequences that are necessary for its efficient localization in the nucleus of infected chicken embryo fibroblasts. These v-rel sequences when added to the normally cytoplasmic protein, beta-galactosidase, directed that protein to the nucleus. A mutation in the v-rel nuclear-localizing sequence did not affect the transforming function, although it did alter the nuclear-localizing function. The addition of a supplemental nuclear-localizing sequence from simian virus 40 large T-antigen to v-rel resulted in the expression of a transforming rel protein which was located exclusively in the nucleus of transformed spleen cells, in contrast to wild-type p59v-rel, which was largely cytoplasmic in transformed spleen cells. Our results support the hypothesis that v-rel encodes a protein which can act either in the nucleus or in the cytoplasm to transform spleen cells.
高度致癌的禽逆转录病毒网状内皮增生症病毒T株（Rev-T）的v-rel癌基因编码的转化蛋白是一种59,000道尔顿的蛋白，即p59v-rel。p59v-rel诱导早期淋巴细胞转化的机制尚不清楚。作为了解v-rel诱导转化机制的一个步骤，我们试图确定p59v-rel的亚细胞作用位点。在本报告中，我们表明p59v-rel含有使其有效定位于受感染鸡胚成纤维细胞核内所必需的序列。当将这些v-rel序列添加到通常位于细胞质的蛋白β-半乳糖苷酶上时，可使该蛋白定位于细胞核。v-rel核定位序列中的一个突变虽改变了核定位功能，但不影响转化功能。将来自猴病毒40大T抗原的一个补充核定位序列添加到v-rel上，导致表达一种转化性rel蛋白，该蛋白仅位于转化脾细胞的细胞核内，而野生型p59v-rel在转化脾细胞中主要位于细胞质中。我们的结果支持这样一种假说，即v-rel编码一种蛋白，该蛋白可在细胞核或细胞质中发挥作用以转化脾细胞。
