title: alpha-fetoprotein as a biologic response modifier: relevance to domain and subdomain structure.
abstract: In the present review, the structure of alpha-fetoprotein (AFP) is discussed in consideration of AFP membership and position in the albuminoid supergene family in relation to other gene family members. Ontogenetic AFP gene expression is then discussed in view of AFP mRNA presence in various tissues at different times during development. The multiple molecular forms of AFP is also presented in relation to published reports of AFP binding proteins and cell surface receptors. The review proceeds on to present AFP as a potential model of a modular/cassette protein based on sequence comparison with cleaved fragments of prohormones and biological response modifiers. Such cleaved fragments could potentially serve as peptide messengers for vascular, neuroendocrine, and digestive biological activities. Following a discussion on fibrin binding and serine proteases, AFP-cytoskeletal, extracellular matrix, and cellular adhesion interactions are considered. AFP as a carrier/transport protein based on structural relationships is further elucidated by examination of the various ligands bound to AFP and its hormone interaction. Since AFP binds heavy metals, the question is posed of whether AFP could function as an antioxidant. An analysis of transcription factors, tumor suppressors, and homeodomain proteins follows, which is interfaced with the concept of programmed cell death in light of amino acid sequence matches detected on the AFP molecule. Emphasis was naturally placed upon the homeodomain protein sequence stretches since AFP is a fetal, phase-specific protein found throughout embryogenesis, histogenesis, and organogenesis. In keeping with histogenesis, a discussion of AFP and eye lens protein development is presented. Finally, AFP sequence analysis presented in light of members of the immunoglobulin superfamily, autoimmune disorders, and various disease states culminates the review. A closing discussion then summarizes regions of presumptive matched protein identities on each of AFP's three domains.
authors.affiliation: Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany 12201, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Mizejewski
mesh_terms: D000818:Animals; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000502:physiology*; D066298:In Vitro Techniques; D017421:Sequence Analysis; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D007155:Immunologic Factors; D000509:alpha-Fetoproteins