A giant protease with potential to substitute for some functions of the proteasome

被引：304

作者：

Geier, E

Pfeifer, G

Wilm, M

Lucchiari-Hartz, M

Baumeister, W

Eichmann, K

Niedermann, G

机构：

[1] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany

[2] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[3] European Mol Biol Lab, D-69117 Heidelberg, Germany

来源：

SCIENCE | 1999年 / 283卷 / 5404期

关键词：

D O I：

10.1126/science.283.5404.978

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：

An alanyl-alanyl-phenylalanyl-7-amino-4-methylcoumarin-hydrolyzing protease particle copurifying with 265 proteasomes was isolated and identified as tripeptidyl peptidase II(TPPII), a cytosolic subtilisin-like peptidase of unknown function. The particle is larger than the 265 proteasome and has a rod-shaped, dynamic supramolecular structure. TPPII exhibits enhanced activity in proteasome inhibitor-adapted cells and degrades polypeptides by exo- as well as predominantly trypsin-like endoproteolytic cleavage. TPPII may thus participate in extralysosomal polypeptide degradation and may in part account for nonproteasomal epitope generation as postulated for certain major histocompatibility complex class I alleles, In addition, TPPII may be able to substitute for some metabolic functions of the proteasome.

引用

收藏

页码：978 / 981

页数：4

相关论文

共 28 条

[11] Lactacystin, a specific inhibitor of the proteasome, induces apoptosis in human monoblast U937 cells [J].

ImajohOhmi, S ;

Kawaguchi, T ;

Sugiyama, S ;

Tanaka, K ;

Omura, S ;

Kikuchi, H .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 217 (03) :1070-1077

[12] How proteolysis drives the cell cycle [J].

King, RW ;

Deshaies, RJ ;

Peters, JM ;

Kirschner, MW .

SCIENCE, 1996, 274 (5293) :1652-1659

[13]

KIRSCHKE H, 1977, ACTA BIOL MED GER, V36, P185

[14] SUPRAMOLECULAR STRUCTURE OF TRIPEPTIDYL PEPTIDASE-II FROM HUMAN-ERYTHROCYTES AS STUDIED BY ELECTRON-MICROSCOPY, AND ITS CORRELATION TO ENZYME-ACTIVITY [J].

MACPHERSON, E ;

TOMKINSON, B ;

BALOW, RM ;

HOGLUND, S ;

ZETTERQVIST, O .

BIOCHEMICAL JOURNAL, 1987, 248 (01) :259-263

[15] Proteasome inhibitors activate stress kinases and induce Hsp72 - Diverse effects on apoptosis [J].

Meriin, AB ;

Gabai, VL ;

Yaglom, J ;

Shifrin, VI ;

Sherman, MY .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (11) :6373-6379

[16] The proteolytic fragments generated by vertebrate proteasomes: Structural relationships to major histocompatibility complex class I binding peptides [J].

Niedermann, G ;

King, G ;

Butz, S ;

Birsner, U ;

Grimm, R ;

Shabanowitz, J ;

Hunt, DF ;

Eichmann, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (16) :8572-8577

[17] MODE OF ACTION TOWARDS OLIGOPEPTIDES AND PROTEINS OF HYDROLASE-H, A HIGH-MOLECULAR-WEIGHT AMINOENDOPEPTIDASE FROM RABBIT SKELETAL-MUSCLE [J].

NISHIMURA, T ;

OKITANI, A ;

KATAKAI, R ;

KATO, H .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1983, 137 (1-2) :23-27

[18] THE UBIQUITIN-PROTEASOME PATHWAY IS REQUIRED FOR PROCESSING THE NF-KAPPA-B1 PRECURSOR PROTEIN AND THE ACTIVATION OF NF-KAPPA-B [J].

PALOMBELLA, VJ ;

RANDO, OJ ;

GOLDBERG, AL ;

MANIATIS, T .

CELL, 1994, 78 (05) :773-785

[19] Ump1p is required for proper maturation of the 20S proteasome and becomes its substrate upon completion of the assembly [J].

Ramos, PC ;

Hockendorff, J ;

Johnson, ES ;

Varshavsky, A ;

Dohmen, RJ .

CELL, 1998, 92 (04) :489-499

[20] INHIBITORS OF THE PROTEASOME BLOCK THE DEGRADATION OF MOST CELL-PROTEINS AND THE GENERATION OF PEPTIDES PRESENTED ON MHC CLASS-I MOLECULES [J].

ROCK, KL ;

GRAMM, C ;

ROTHSTEIN, L ;

CLARK, K ;

STEIN, R ;

DICK, L ;

HWANG, D ;

GOLDBERG, AL .

CELL, 1994, 78 (05) :761-771