Alpha-fetoprotein signal sequences: a proposed mechanism for subcellular localization and organelle targeting.
Alpha-fetoprotein (AFP) is an oncofetal protein, classified in an "albuminoid" superfamily (with albumin and Vitamin-D binding (Gc) protein) comprising molecules with three characteristic globular domains. The cellular uptake and internalization of AFP and its subcellular compartmentalization has previously been reported in a multitude of cell types. Studies have also emerged which have detected and characterized binding proteins complexed to AFP in various cell membranes and intracellular compartments. However, the literature is devoid of any attempts to relate these binding proteins to possible intracellular trafficking interactions of AFP. Recombinant DNA mutation/deletion technology has provided a means to pinpoint the amino acid sequence location of organelle localization signals on various transcription factors and/or receptors. Several subdomain regions on AFP have been reported to mimic heptad dimerization regions of the steroid/thyroid nuclear receptors. In light of these transcription factor-like docking motifs reported for AFP, the present report purposes various subdomain regions which might constitute basic amino acid sequences resembling recognition signals for binding (dimerizing) proteins. AFP appears to possess multiple prototypic amino acid sequence cassettes on each domain which consist of (i) classical short, compact sequences found on both steroid and thyroid receptors; (ii) proto-signals resembling a steroid receptor type; and (iii) degenerative signal sequence similar to the thyroid/retinoic acid receptor type. The concepts identifying binding or escort proteins for AFP together with organelle signal sequences on AFP have been reconciled in a composite hypothesis to formulate a mechanism which could account for some of the growth-regulating properties described for AFP during the last decade.
D000595:Amino Acid Sequence; D004848:Epithelium / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology*; D008969:Molecular Sequence Data; D015388:Organelles / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D015398:Signal Transduction; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D006133:Growth Substances; D018000:Receptors, Peptide; D000509:alpha-Fetoproteins; C042144:alpha-fetoprotein receptor, human