The extracellular domains of death ligands and those of death receptors are closely related to many serious human
diseases through the initiation of apoptosis. Recombinant production of the extracellular domains has been investigated
due to demand for a large amount of purified samples, which are a prerequisite for their biochemical characterization
and constitute the fundamentals of medical applications. This review focuses on the recombinant production of extracellular
domains of the major members of death ligand and death receptor families using non-mammalian expression
systems with an emphasis on Fas ligand and Fas receptor. In contrast to the efficient production of the functional extracellular
domains of TRAIL, TNFα and LTα by intracellular expression systems using Escherichia coli or Pichia pastoris,
that of Fas ligand requires the secretory expression systems using P. pastoris or Dictyostelium discoideum, and the productivity
in P. pastoris was largely dependent on tag sequence, potential N-glycosylation site and expressed protein region.
On the other hand, the exploitation of insect cell systems is generally useful for the preparation of functional extracellular
domains of death receptors containing many disulfide bridges in the absence of extended secondary structure,
and a Bombyx mori larvae secretion system presented a superior productivity for human Fas receptor extracellular domain.
Based on the results obtained so far, further efforts should be devoted to the artificial control of death ligand – death receptor
interactions in order to make a contribution to medicine, represented by the development of novel biopharmaceuticals.
Keywords: Apoptosis, biopharmaceuticals, death ligand, death receptor, expression system, heterologous production, recombinant protein, structural feature, autoimmune diseases, homeostasis
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