Polypeptide Hormones and Chromatin-Associated Proteins Act as Acceptors for Cholera Toxin-Catalyzed ADP-Ribosylation |
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Authors: | J B Trepel D-M Chuang N H Neff |
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Institution: | Laboratory of Preclinical Pharmacology. National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D.C. 20032, U.S.A. |
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Abstract: | Abstract: Cholera toxin catalyzed the ADP-ribosylation of the pituitary protein hormones thyrotropin (TSH), lutropin (LH), follitropin (FSH), human chorionic gonadotropin (hCG). and corticotropin (ACTH)1–24, and ADP-ribosylation of the basic proteins histone subfraction H1 and protamine. Casein and phosvitin, acidic nuclear proteins, did not act as acceptors for toxin-catalyzed ADP-ribosylation. The isolated TSH A and B subunits were tested for their ADP-ribose acceptor activity. The TSH A subunit showed fourfold greater ADP-ribose acceptor activity than the TSH B subunit. The ADP-ribose acceptor protein protamine was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis following incubation with cholera toxin under ADP-ribosylating conditions. 3H]ADP-ribose incorporated into protein from 3H]NAD migrated with the acceptor protein protamine. In the absence of added acceptor protein, the 3H]ADP-ribose incorporated into protein migrated with the A1 fragment of cholera toxin. Cholera toxin A and B subunits were isolated and tested for their ability to catalyze the transfer of ADP-ribose to protamine. The cholera toxin A subunit showed 50-fold greater ADP-ribosyltransferase activity than the B subunit. Our data indicate that a variety of adenohypophyseal hormones and regulatory proteins act as acceptors for toxin-catalyzed ADP-ribosylation. These studies may help in understanding the role of endogenous ADP-ribosyltransferases and the physiological effects of this modification of protein. |
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Keywords: | ADP-ribosylation Cholera toxin Pituitary hormones ACTH Histone Protamine |
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