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.

Abstract:

: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 mu-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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Tsubuki S,Saito Y,Kawashima S

doi

10.1016/0014-5793(94)00388-2

subject

Has Abstract

pub_date

1994-05-16 00:00:00

pages

229-33

issue

2-3

eissn

0014-5793

issn

1873-3468

pii

0014-5793(94)00388-2

journal_volume

344

pub_type

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