Survey of Functional Activities of Alpha-fetoprotein Derived Growth Inhibitory Peptides: Review and Prospects

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.