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 subdomain regions on AFP have been previously proposed to serve as dimerization interfaces for nuclear receptors or perhaps other co-factors/inhibitors. The cellular uptake and internalization of AFP together with its subcellular compartmentalization is now well documented in a variety of cell types. A myriad of reports have emerged which have detected, identified, and characterized various binding proteins associated with AFP in different cellular compartments. However, the literature is devoid of any attempts to summarize, categorize, and relate these proteins to the various physiological activities attributed to this fetal protein. It is conceivable that AFP could interact and/or bind cytoplasmic chaperone proteins that normally escort nuclear factors or transcription co-factors through the cytoplasm toward organelle interfaces. A dual concept proposing binding or escort proteins for AFP together with subdomain dimerization interfaces on the AFP molecule can be reconciled into a composite hypothesis to formulate a rationale for the growth regulating properties ascribed to AFP during the last decade. Thus, AFP might serve as a modulator/modifier of various cell growth regulatory pathways during embryonic and fetal development in vertebrates.
Mizejewski
G J
GJ
Laboratory of Human Genetics, Wadsworth Center for Labs & Research, NYS Dept. of Health, Albany 12201.
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D018000:Receptors, Peptide / Q000032:analysis; D000509:alpha-Fetoproteins / Q000378:metabolism*
D002352:Carrier Proteins; D018000:Receptors, Peptide; D000509:alpha-Fetoproteins; C042144:alpha-fetoprotein receptor, human