La autoantigen is cleaved in the COOH terminus and loses the nuclear localization signal during apoptosis
La autoantigen is cleaved in the COOH terminus and loses the nuclear localization signal during apoptosis
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DOI：
10.1074/jbc.m003673200
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发表时间：
2000-11-03
影响因子：
4.8
通讯作者：
Sagara, J
中科院分区：
文献类型：
--
作者：
Ayukawa, K;Taniguchi, S;Sagara, J
La自身抗原是一种47kda的核蛋白，与新生聚合酶III转录物和许多病毒rna结合。我们发现La蛋白在喜树碱或依托波苷处理的人白血病HL-60细胞凋亡过程中被裂解产生一个43 kda的片段。免疫荧光显微镜观察发现，HL-60细胞凋亡过程中细胞质中La蛋白水平升高。此外，紫外线照射HeLa细胞导致La蛋白在凋亡过程中发生裂解和重新分布。一些证据表明，La蛋白在COOH末端的Asp-374处被caspase-3或密切相关的蛋白酶切割。当La蛋白全长（La）和cooh末端截断（La Delta C374）形式与绿色荧光蛋白（GFP）融合表达时，GFP-La Delta C374主要在细胞质中表达，而GFP-La则定位于细胞核中。这些结果表明，La蛋白在切割过程中失去了位于COOH末端的核定位信号，从而在细胞凋亡过程中被重新分配到细胞质中。
La autoantigen is a 47-kDa nuclear protein that binds to nascent polymerase III transcripts and a number of viral RNAs. We show that La protein was cleaved to generate a 43-kDa fragment during apoptosis of human leukemic HL-60 cells treated with camptothecin or etoposide. Immunofluorescence microscopy showed that the La protein level was increased in the cytoplasm during apoptosis of HL-60 cells. In addition, UV irradiation of HeLa cells led to the cleavage and redistribution of La protein upon apoptosis. Several lines of evidence show that La protein is cleaved by caspase-3 or closely related proteases at Asp-374 in the COOH terminus. When the full-length (La) and COOH-terminally truncated (La Delta C374) forms of La protein were expressed as fusion proteins with green fluorescence protein (GFP), GFP-La Delta C374 was predominantly cytoplasmic, whereas GFP-La was localized in the nucleus. These results suggest that La protein loses the nuclear localization signal residing in the COOH terminus upon cleavage and is thus redistributed to the cytoplasm during apoptosis.