Purification and characterization of an endogenous inhibitor specific to the Z-Leu-Leu-Leu-MCA degrading activity in proteasome and its identification as heat-shock protein 90

We previously identified a benzyloxycarbonyl(Z)-Leu-Leu-Leu-4-methylcoumaryl-7-amide (ZLLL-MCA) degrading activity in proteasome as a candidate for the regulator of neurite outgrowth. As its counterpart, we purified a protein from bovine brain that specifically inhibits the ZLLL-MCA degrading activi...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	FEBS letters 1994-05, Vol.344 (2), p.229-233
Hauptverfasser:	Tsubuki, Satoshi, Saito, Yumiko, Kawashima, Seiichi
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Sequence Animals Boc-VLK-MCA, tertiary butyloxycarbonyl-Val-Leu-Lys-4-methylcoumaryl-7-amide Brain - enzymology buffer A, 20 mM Tris-HCl, pH 7.0, containing 10% glycerol buffer B, 20 mM Tris-HCl, pH 7.5, containing 5 mM EDTA and 10% glycerol Cattle Electrophoresis, Polyacrylamide Gel Endopeptidases - metabolism Fluorescent Dyes Heat-shock protein 90 Heat-Shock Proteins - chemistry Heat-Shock Proteins - isolation & purification HSP, heat-shock protein MCA, 4-methylcoumaryl-7-amide Molecular Sequence Data Molecular Weight Neurite outgrowth Oligopeptides - metabolism PAGE, polyacrylamide gel electrophoresis Protease Inhibitors - chemistry Protease Inhibitors - isolation & purification Protease Inhibitors - pharmacology Proteasome Proteasome inhibitor PVDF, polyvinylidene difluoride Sequence Analysis SucLLVY-MCA, succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide Z, benzyloxycarbonyl ZLLE-NA, benzyloxycarbonyl-Leu-Leu-Glu-β-naphthyl-amide ZLLL-MCA, benzyloxycarbonyl-Leu-Leu-4-methylcoumaryl-7-amide ZLLLal, benzyloxycarbonyl-Leu-Leu-leucinal
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	We previously identified a benzyloxycarbonyl(Z)-Leu-Leu-Leu-4-methylcoumaryl-7-amide (ZLLL-MCA) degrading activity in proteasome as a candidate for the regulator of neurite outgrowth. As its counterpart, we purified a protein from bovine brain that specifically inhibits the ZLLL-MCA degrading activity in proteasome. This protein is heat stable and has no effect on the other catalytic activities in proteasome, or on the activities of trypsin, chymotrypsin, or m- and μ-calpains either. The molar ratio of inhibitor-to-proteasome that inhibits 50% of the ZLLL-MCA degrading activity of proteasome is 1:1. The inhibitory mechanism of the inhibitor against proteasome is non-competitive. Finally, the inhibitor was identified as heat-shock protein 90 (HSP90) by partial amino acid sequencing and immunodetection. The results suggest that HSP90 initiates neurite outgrowth through the inhibition of the ZLLL-MCA degrading activity in proteasome.
ISSN:	0014-5793 1873-3468
DOI:	10.1016/0014-5793(94)00388-2