Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor.

Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor.
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DOI:
10.1016/s0021-9258(17)39652-7
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发表时间:
1985-06
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Kay Luad;Billie M. Moats-StaatsQ;James;Simmons;Eileen HoytQ;A. D'ercole;F. Martin;Judson;-J.;Van WykQ
Kay Luad;Billie M. Moats-StaatsQ;James;Simmons;Eileen HoytQ;A. D'ercole;F. Martin;Judson;-J.;Van WykQ
中科院分区:
其他
文献类型:
--
作者:
Kay Luad;Billie M. Moats-StaatsQ;James;Simmons;Eileen HoytQ;A. D'ercole;F. Martin;Judson;-J.;Van WykQ

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泛素是由76个氨基酸组成的蛋白质,其序列在从无脊椎动物到哺乳动物的整个进化过程中高度保守。它是一种细胞质和核蛋白。在细胞质中,它参与ATP依赖性非溶酶体蛋白水解。在细胞核中,泛素与组蛋白2A结合,并可能在调节染色质结构和/或调节转录活性中发挥作用。在试图鉴定编码生长调节素-C(胰岛素样生长因子I)的cDNA的过程中,我们用对应于生长调节素-C的B链的一部分的17个碱基的寡核苷酸的混合物筛选了人胎肝cDNA文库。混合物中的一个寡核苷酸与两个编码泛素的cDNA杂交,尽管存在2个碱基对的错配。350和516碱基对cDNA的核苷酸序列分析显示,它们对应于相同的泛素mRNA。516个碱基对的cDNA的编码序列开始于泛素序列的氨基酸5,并编码泛素的氨基酸5至76、80个氨基酸的羧基末端延伸、3'非翻译区和poly(A)尾。泛素作为前体合成的发现提高了前体序列在泛素或泛素前体的区室化中可能是重要的可能性。从人肝脏和各种大鼠组织中提取的poly(A)RNA中的泛素mRNA的分析揭示,在人类中有三种不同的mRNA编码泛素,在大鼠中有四种mRNA编码泛素。
Ubiquitin is a 76-amino acid protein whose sequence is highly conserved throughout evolution from invertebrates to mammals. It is both a cytoplasmic and nuclear protein. In the cytoplasm it is involved in ATP-dependent nonlysosomal proteolysis. In the nucleus, ubiquitin is conjugated to histone 2A and may play a role in regulation of chromatin structure and/or regulation of transcriptional activity. During attempts to identify a cDNA encoding somatomedin-C (insulin-like growth factor I) we screened a fetal human liver cDNA library with a mixture of 17 base oligonucleotides corresponding to a portion of the B chain of somatomedin-C. One oligonucleotide of the mixture hybridized to two cDNAs encoding ubiquitin despite a 2-base pair mismatch. Nucleotide sequence analyses of the 350- and 516-base pair cDNAs revealed that they correspond to the same ubiquitin mRNA. The coding sequence of the 516-base pair cDNA begins at amino acid 5 of the ubiquitin sequence and encodes amino acids 5 through 76 of ubiquitin, an 80-amino acid carboxy-terminal extension, a 3' untranslated region, and a poly(A) tail. The finding that ubiquitin is synthesized as a precursor raises the possibility that the precursor sequence may be important in compartmentalization of ubiquitin or ubiquitin precursors. Analyses of ubiquitin mRNAs in poly(A) RNA extracted from human liver and various rat tissues reveals that there are three distinct mRNAs encoding ubiquitin in humans and four mRNAs in the rat.