Identification of early pregnancy factor as chaperonin 10: implications for understanding its role.
Early pregnancy factor (EPF) is a secreted substance with growth regulatory and immunomodulatory properties. It is required for successful establishment of pregnancy and for proliferation of both normal and neoplastic cells, in vivo and in vitro. The rosette inhibition test was used as a bioassay, and the appearance of EPF in serum in the very early stages of pregnancy (in mice, within 4-6 h of mating) was first described two decades ago. However, because of the difficulty of this bioassay and the paucity of EPF in biological materials, the primary structure of the molecule has been identified only recently. Seventy per cent of the amino acid sequence of EPF derived from human platelets was determined. With the exception of a single residue, this was identical to the sequence of rat mitochondrial chaperonin 10 (cpn10). Cpn10 is a heat shock protein that functions as a molecular chaperone. It binds to and stabilizes cpn60 and, in concert, these molecules mediate protein folding in mitochondria, chloroplasts and bacteria. Characterizing EPF as an extracellular form of cpn10 raises unprecedented questions about the mechanism of action. It may be that, as a molecular chaperone in the extracellular compartment, EPF can functionally modify other proteins, serving as a regulator of regulators.
Cavanagh
A C
AC
University of Queensland, Department of Surgery, Royal Brisbane Hospital, Australia.
D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D001681:Biological Assay; D018835:Chaperonin 10 / Q000302:isolation & purification / Q000502:physiology*; D005260:Female; D006801:Humans; D010455:Peptides / Q000302:isolation & purification / Q000502:physiology*; D011247:Pregnancy; D011257:Pregnancy Proteins; D012397:Rosette Formation; D013491:Suppressor Factors, Immunologic
D000276:Adjuvants, Immunologic; D018835:Chaperonin 10; D010455:Peptides; D011257:Pregnancy Proteins; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor