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.
Leibovitz
D
D
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Koch
Y
Y
Pitzer
F
F
Fridkin
M
M
Dantes
A
A
Baumeister
W
W
Amsterdam
A
A
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