Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products.
Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products.
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人胸腺肽α基因家族的分离和部分测序。
DOI：
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发表时间：
1989
影响因子：
4.8
通讯作者：
S. L. Berger
中科院分区：
文献类型：
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作者：
W. Eschenfeldt;R. E. Manrow;M. Krug;S. L. Berger
据信胸腺素原α和胸腺素α 1是胸腺衍生的激素样物质，具有在细胞外执行的免疫调节功能。这些功能与不编码氨基末端信号肽或几个连续疏水残基的全长cDNA克隆的存在不一致。对胸腺素α原mRNA和基因进行了研究，以寻找该蛋白分泌形式的证据。前胸腺素α mRNA只定位于自由的，而不是膜结合的，多核糖体。在筛选共2 × 10（6）个克隆的粘粒和质粒文库后，鉴定出由六个成员组成的基因家族。所有基因的5 '端序列信息表明，没有一个编码氨基端信号肽。其中一个基因显然是通过选择性剪接产生两个胸腺素原α mRNA，其中一个相对于另一个具有额外的内部谷氨酸密码子。将其余五个基因的翻译核酸序列与mRNA中编码的序列进行比较，发现前50个氨基酸具有30-98%的同源性。这五个基因似乎是加工基因和/或假基因。胸腺素原α mRNA在游离多聚核糖体上的定位，以及基因的部分核苷酸序列，强烈表明胸腺素原α具有细胞内功能。因此，胸腺素原α及其肽衍生物在引入免疫功能测定时作为外源性物质的可能性必须提高。
Prothymosin alpha and thymosin alpha 1 are believed to be thymus-derived, hormone-like materials with immunomodulatory functions performed outside the cell. These functions are inconsistent with the existence of a full length cDNA clone that does not encode an amino-terminal signal peptide or several consecutive hydrophobic residues. A study of the prothymosin alpha mRNAs and genes was undertaken in search of evidence for secreted forms of the protein. Prothymosin alpha mRNA was localized exclusively on free, rather than membrane-bound, polysomes. Upon screening cosmid and plasmid libraries totaling 2 X 10(6) clones, a gene family consisting of six members was identified. Sequence information from the 5'-ends of all the genes indicated that none encodes an amino-terminal signal peptide. One of the genes, apparently by means of alternate splicing, gives rise to two prothymosin alpha mRNAs, one of which has an additional internal glutamic acid codon with respect to the other. Comparison of the translated nucleic acid sequences of the five remaining genes with those encoded in the mRNAs revealed 30-98% homology in the first 50 amino acids. These five genes appear to be processed genes and/or pseudogenes. The localization of prothymosin alpha mRNAs on free polysomes, together with the partial nucleotide sequences of the genes, strongly suggest an intracellular function for prothymosin alpha. Therefore, the possibility must be raised that prothymosin alpha and its peptide derivatives act as xenobiotics when introduced into assays of immune function.