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首页> 外文期刊>Cell biology international. >Review and proposed action of alpha-fetoprotein growth inhibitory peptides as estrogen and cytoskeleton-associated factors.
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Review and proposed action of alpha-fetoprotein growth inhibitory peptides as estrogen and cytoskeleton-associated factors.

机译：审查和建议的作用甲胎蛋白生长抑制肽作为雌激素和细胞骨架相关因子。

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The (H) human growth-promoting factor, alpha-fetoprotein (AFP), has been reported to possess a growth inhibitory motif as an occult epitope in the compactly folded circulating form of the protein. Intermediate unfolded forms of the human HAFP molecule induced by stress, shock, and high ligand concentrations have revealed the presence of an encrypted growth-suppressive segment on the third domain of HAFP. A purified linear synthetic 34-mer segment termed the "growth inhibitory peptide" (GIP) exhibits various oligomeric forms with complex aggregation behaviors, in which dominant trimeric forms were found to be suppressive in assays of estrogen-induced growth. While several amino acid analogs of the cysteines of the GIP retained inhibitory activity, heavy metal binding and pre-incubation of the peptides with a variety of cations and hormone ligands were found to influence the outcomes of growth bioassays. Smaller segments of the original 34-mer were each found to display growth activities of their own, with the middle segment (P149b) also showing hydrophobic dye-binding properties. Studies of amino acid sequence identity further revealed that the GIP sequences displayed identity/similarity matches to both cytoplasmic and nucleus-cytoskeleton-associated proteins, and experimental evidence served to support these findings. That is, the peptide was capable of modulating tubulin polymerization, cell shape, and cell-surface aggregation phenomena reminiscent of a microtubule-associated protein. Immunofluorescence studies further pinpointed the localization of the GIP to cytoplasmic regions of high cytoskeletal density in the cell. Because of the involvement of the GIP in experimental models of the estrogen receptor/cytoskeleton, a mechanism of action is forwarded in which the linear GIP is proposed to be a G-coupled receptor binding ligand that is translocated across the plasma membrane via receptor-mediated endocytosis. Thus, it was predicted that the linear GIP and possibly its peptidic segments serve as decoy ligands to cell-surface receptors in order to gain access to the cytoplasmic compartment of the cell.
机译：（H）人类生长促进因子，甲胎蛋白（AFP），据报道以紧密折叠的蛋白质循环形式具有作为隐匿表位的生长抑制基序。由压力，休克和高配体浓度诱导的人类HAFP分子的中间未折叠形式表明，在HAFP的第三个结构域上存在一个加密的生长抑制片段。纯化的线性合成34-mer节段，称为“生长抑制肽”（GIP），表现出各种具有复杂聚集行为的寡聚形式，其中主要的三聚体形式在雌激素诱导的生长测定中被抑制。虽然GIP半胱氨酸的几种氨基酸类似物保留了抑制活性，但发现重金属结合以及肽与各种阳离子和激素配体的预温育会影响生长生物测定的结果。发现最初的34-mer的较小部分各自显示其自身的生长活性，而中间部分（P149b）也显示出疏水性染料结合特性。氨基酸序列同一性的研究进一步表明，GIP序列与胞质蛋白和细胞核骨架相关蛋白均显示出同一性/相似性，实验证据支持了这些发现。也就是说，该肽能够调节微管蛋白聚合，细胞形状和细胞表面聚集现象，使人联想到微管相关蛋白。免疫荧光研究进一步指出了GIP在细胞中高细胞骨架密度的胞质区域的定位。由于GIP参与了雌激素受体/细胞骨架的实验模型，因此提出了一种作用机制，其中线性GIP被认为是一种G偶联的受体结合配体，通过受体介导的方式跨质膜转运内吞作用。因此，据预测，线性GIP及其可能的肽段充当细胞表面受体的诱饵配体，以便进入细胞的细胞质区室。

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