ALPHA-FETOPROTEIN BINDING-PROTEINS - IMPLICATIONS FOR TRANSMEMBRANE PASSAGE AND SUBCELLULAR-LOCALIZATION

Alpha-fetoprotein (AFP) is an oncofetal protein classified in a super- family together with albumin and Vitamin-D binding (Gc) protein which present as globular proteins comprised of three domains. Several subdo main regions on AFP have been previously proposed to serve as dimeriza tion interfaces for nuclear receptors or perhaps other co-factors/inhi bitors. The cellular uptake and internalization of AFP together with i ts subcellular compartmentalization is now well documented in a variet y of cell types. A myriad of reports have emerged which have detected, identified, and characterized various binding proteins associated wit h AFP in different cellular compartments. However, the literature is d evoid of any attempts to summarize, categorize, and relate these prote ins to the various physiological activities attributed to this fetal p rotein. It is conceivable that AFP could interact and/or bind cytoplas mic chaperone proteins that normally escort nuclear factors or transcr iption co-factors through the cytoplasm toward organelle interfaces. A dual concept proposing binding or escort proteins for AFP together wi th subdomain dimerization interfaces on the AFP molecule can be reconc iled into a composite hypothesis to formulate a rationale for the grow th regulating properties ascribed to AFP during the last decade. Thus, AFP might serve as a modulator/modifier of various cell growth regula tory pathways during embryonic and fetal development in vertebrates.