FORMATION OF THE ALPHA(1)-MICROGLOBULIN CHROMOPHORE IN MAMMALIAN AND INSECT CELLS - A NOVEL POSTTRANSLATIONAL MECHANISM

alpha(1)-Microglobulin is an immunosuppressive plasma protein synthesized by the liver. The isolated protein is yellow-brown, but the hypothetical chromophore has not yet been identified. In this work, it is shown that a human liver cell line, HepG2, grown in a completely synthetic and serum-free medium, secretes alpha(1)-microglobulin which is also yellow-brown, suggesting a de novo synthesis of the chromophore by the cells. alpha(1)-Microglobulin isolated from the culture medium of insect cells transfected with the gene for rat alpha(1)-microglobulin is also yellow-brown, suggesting that the gene carries information about the chromophore. Reduction and alkylation or removal of N- or O-linked carbohydrates by glycosidase treatment did not reduce the colour intensity of the protein. An internal dodecapeptide (amino acid positions 70-81 in human alpha(1)-microglobulin) was also yellow-brown. The latter results indicate that the chromophore is linked to the polypeptide. In conclusion, the results suggest that the alpha(1)-microglobulin gene carries information activating a post-translational protein modification mechanism which is present in mammalian and insect cells.