ALPHA-FETOPROTEIN AS A BIOLOGIC RESPONSE MODIFIER - RELEVANCE TO DOMAIN AND SUBDOMAIN STRUCTURE

In the present review, the structure of cu-fetoprotein (AFP) is discus sed 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 m olecular forms of AFP is also presented in relation to published repor ts of AFP binding proteins and cell surface receptors. The review proc eeds on to present AFP as a potential model of a modular/cassette prot ein based on sequence comparison with cleaved fragments of prohormones and biological response modifiers. Such cleaved fragments could poten tially serve as peptide messengers for vascular, neuroendocrine, and d igestive biological activities. Following a discussion on fibrin bindi ng and serine proteases, AFP-cytoskeletal, extracellular matrix, and c ellular adhesion interactions are considered. AFP as a carrier/transpo rt protein based on structural relationships is further elucidated by examination of the various ligands bound to AFP and its hormone intera ction. Since AFP binds heavy metals, the question is posed of whether AFP could function as an antioxidant. An analysis of transcription fac tors, tumor suppressors, and homeodomain proteins follows, which is in terfaced with the concept of programmed cell death in light of amino a cid sequence matches detected on the AFP molecule. Emphasis was natura lly placed upon the homeodomain protein sequence stretches since AFP i s a fetal, phase-specific protein found throughout embryogenesis, hist ogenesis, and organogenesis. In keeping with histogenesis, a discussio n of AFP and eye lens protein development is presented. Finally, AFP s equence analysis presented in light of members of the immunoglobulin s uperfamily, autoimmune disorders, and various disease states culminate s the review. A closing discussion then summarizes regions of presumpt ive matched protein identities on each of AFP's three domains.