Sequential degradation of the neuropeptide gonadotropin-releasing hormone by the 20 S granulosa cell proteasomes.
The decapeptide gonadotropin-releasing hormone (GnRH) is degraded by the 20 S multicatalytic proteinase complex (proteasome EC 3.4.99.46), purified from ovarian granulosa cells, at the Tyr5-Gly6 bond and to a lesser extent at the Gly6-Leu7 bond, when incubated for 2 h at 37 degrees C. Further cleavage, at Trp3-Ser4 and Ser4-Tyr5 bonds of the neurohormone occurs only subsequently to the appearance of the initial N-terminal degradation products, (1-5)GnRH and (1-6)GnRH. Our results suggest that the sequential degradation of GnRH can serve as an important mechanism for the rapid termination of its biological activity in target cells.
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
D
D
Leibovitz
Y
Y
Koch
F
F
Pitzer
M
M
Fridkin
A
A
Dantes
W
W
Baumeister
A
A
Amsterdam
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006107:Granulosa Cells / Q000201:enzymology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010902:Pituitary Gland / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex; D051381:Rats
D009097:Multienzyme Complexes; D010446:Peptide Fragments; D007987:Gonadotropin-Releasing Hormone; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex