A NOVEL HETERODIMERIC CYSTEINE PROTEASE IS REQUIRED FOR INTERLEUKIN-1-BETA PROCESSING IN MONOCYTES

被引：2193

作者：

THORNBERRY, NA

BULL, HG

CALAYCAY, JR

CHAPMAN, KT

HOWARD, AD

KOSTURA, MJ

MILLER, DK

MOLINEAUX, SM

WEIDNER, JR

AUNINS, J

ELLISTON, KO

AYALA, JM

CASANO, FJ

CHIN, J

DING, GJF

EGGER, LA

GAFFNEY, EP

LIMJUCO, G

PALYHA, OC

RAJU, SM

ROLANDO, AM

SALLEY, JP

YAMIN, TT

LEE, TD

SHIVELY, JE

MACCROSS, M

MUMFORD, RA

SCHMIDT, JA

TOCCI, MJ

机构：

[1] MERCK SHARP & DOHME LTD, DEPT MOLEC IMMUNOL, POB 2000, RAHWAY, NJ 07065 USA

[2] MERCK SHARP & DOHME LTD, DEPT BIOCHEM, RAHWAY, NJ 07065 USA

[3] MERCK SHARP & DOHME LTD, DEPT BIOCHEM & MOLEC PATHOL, RAHWAY, NJ 07065 USA

[4] MERCK SHARP & DOHME LTD, DEPT MED CHEM RES, RAHWAY, NJ 07065 USA

[5] MERCK SHARP & DOHME LTD, DEPT CELLULAR & MOLEC PHARMACOL, RAHWAY, NJ 07065 USA

[6] MERCK SHARP & DOHME LTD, DEPT BIOCHEM PROC RES & DEV, RAHWAY, NJ 07065 USA

[7] MERCK SHARP & DOHME LTD, DEPT BIOL DATA, RAHWAY, NJ 07065 USA

[8] CITY HOPE NATL MED CTR, BECKMAN RES INT, DUARTE, CA 91010 USA

来源：

NATURE | 1992年 / 356卷 / 6372期

关键词：

D O I：

10.1038/356768a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Interleukin-1-beta (IL-1-beta)-converting enzyme cleaves the IL-1-beta precursor to mature IL-1-beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1-beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1-beta, indicating that it is a potential therapeutic target.

引用

页码：768 / 774

页数：7

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[1] COMPARATIVE-ANALYSIS OF VIRAL CYSTEINE PROTEASE STRUCTURAL MODELS [J].