Mizejewskia Gerald J, Butterstein George
Division of Molecular Medicine, Wadsworth Center, New York State Dept. of Health, PO Box 509, Albany, NY 12201, USA.
Curr Protein Pept Sci. 2006 Feb;7(1):73-100. doi: 10.2174/138920306775474130.
Alpha-fetoprotein (AFP), known largely as a growth-promoting agent, possesses a growth-inhibitory motif recently identified as an occult epitopic segment in the third domain. The present study reviews the multiple biological activities of this AFP-derived peptide segment termed the Growth Inhibitory Peptide (GIP), which is a 34-amino acid fragment taken directly from the full-length 590 amino acid molecule. The GIP segment has been chemically synthesized, purified, characterized, and subjected to a variety of bioassays. The GIP has a proven record of growth suppression in both fetal and tumor cells, but not in normal adult cells. Even though the mechanism of action has not been completely elucidated, GIP participates in various biological activities such as endocytosis, angiogenesis, and cytoskeleton-induced/cell shape changes. In this review, a survey of the functional roles of the GIP is presented which encompasses multiple organizational levels of GIP involvement, including the 1) organism, 2) organ, 3) tissue, 4) cell, 5) plasma membrane, 6) cytoplasm, and 7) the nucleus. At the cell membrane interface, the actions of GIP are discussed concerning cell aggregation, agglutination, adhesion, and migration in light of GIP serving as a possible decoy ligand and/or soluble receptor. Regarding cytosolic activities, GIP has been reported to inhibit various cytoplasmic enzyme activities, modulate apoptotic events, and regulate cytoplasmic signal transduction (MAP kinase) cascades. Concerning the nuclear compartment, GIP is capable of complexing with the estrogen receptor and binding estradiol, but does not affect estradiol-induced estrogen receptor transcription. In overview, efforts were made to review the multiple biological activities reported for GIP in order to prioritize likely physiological activities and present an updated consensus of functional roles for this AFP-derived peptide.
甲胎蛋白（AFP）在很大程度上被认为是一种生长促进剂，但其最近被发现具有一个生长抑制基序，该基序位于第三结构域，是一个隐匿的表位片段。本研究综述了这种源自AFP的肽段——生长抑制肽（GIP）的多种生物学活性。GIP是一个由34个氨基酸组成的片段，直接取自全长590个氨基酸的分子。GIP片段已通过化学合成、纯化、表征，并进行了多种生物测定。GIP在胎儿细胞和肿瘤细胞中均有生长抑制的记录，但在正常成年细胞中则无此作用。尽管其作用机制尚未完全阐明，但GIP参与了多种生物学活动，如内吞作用、血管生成以及细胞骨架诱导的/细胞形状变化。在本综述中，对GIP的功能作用进行了概述，涵盖了GIP参与的多个组织水平，包括1）生物体、2）器官、3）组织、4）细胞、5）质膜、6）细胞质和7）细胞核。在细胞膜界面，鉴于GIP可能作为诱饵配体和/或可溶性受体，讨论了其在细胞聚集、凝集、黏附和迁移方面的作用。关于胞质活性，据报道GIP可抑制多种细胞质酶活性、调节凋亡事件并调控细胞质信号转导（丝裂原活化蛋白激酶）级联反应。关于细胞核区室，GIP能够与雌激素受体结合并结合雌二醇，但不影响雌二醇诱导的雌激素受体转录。总的来说，本文努力综述了已报道的GIP的多种生物学活性，以便对可能的生理活性进行排序，并给出这种源自AFP的肽的功能作用的最新共识。
