INACTIVATION OF NF-KAPPA-B INHIBITOR I-KAPPA-B-ALPHA - UBIQUITIN-DEPENDENT PROTEOLYSIS AND ITS DEGRADATION PRODUCT

被引:58
作者
LI, CCH [1 ]
DAI, RM [1 ]
LONGO, DL [1 ]
机构
[1] NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702
关键词
D O I
10.1006/bbrc.1995.2465
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In most cells, the inactive dimeric NF-kappa B complexes an retained in the cytoplasm by binding to a group of inhibitory proteins, I kappa B. In response to extracellular stimuli, I kappa B is rapidly phosphorylated and degraded, thus, liberating the active NF-kappa B. To investigate the mechanisms involved, we have developed a cell-free system to study the degradation of the prototype I kappa B protein, I kappa B alpha. In this in vitro assay, ubiquitin, proteasome-containing S100 fraction and ATP are required for the proteolysis of I kappa B alpha. Both bound and free forms of I kappa B alpha isolated from intact cells can be degraded through this pathway. We also identified polyubiquitinated I kappa B alpha molecules and N-terminal truncated I kappa B alpha degradation product(s) both in vivo and in vitro. We conclude that the inactivation of I kappa B alpha occurs through a series of processes including phosphorylation, ATP-dependent ubiquitin conjugation and proteasome-mediated proteolysis. (C) 1995 Academic Press, Inc.
引用
收藏
页码:292 / 301
页数:10
相关论文
共 34 条
[11]   GENERATION OF P50 SUBUNIT OF NF-KAPPA-B BY PROCESSING OF P105 THROUGH AN ATP-DEPENDENT PATHWAY [J].
FAN, CM ;
MANIATIS, T .
NATURE, 1991, 354 (6352) :395-398
[12]   INDUCIBLE PHOSPHORYLATION OF I-KAPPA-B-ALPHA IS NOT SUFFICIENT FOR ITS DISSOCIATION FROM NF-KAPPA-B AND IS INHIBITED BY PROTEASE INHIBITORS [J].
FINCO, TS ;
BEG, AA ;
BALDWIN, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) :11884-11888
[13]   DORSAL, A DROSOPHILA REL-LIKE PROTEIN, IS PHOSPHORYLATED UPON ACTIVATION OF THE TRANSMEMBRANE PROTEIN TOLL [J].
GILLESPIE, SKH ;
WASSERMAN, SA .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (06) :3559-3568
[14]  
GRILLI M, 1993, INT REV CYTOL, V143, P1
[15]   CHARACTERIZATION OF AN IMMEDIATE-EARLY GENE INDUCED IN ADHERENT MONOCYTES THAT ENCODES I-KAPPA-B-LIKE ACTIVITY [J].
HASKILL, S ;
BEG, AA ;
TOMPKINS, SM ;
MORRIS, JS ;
YUROCHKO, AD ;
SAMPSONJOHANNES, A ;
MONDAL, K ;
RALPH, P ;
BALDWIN, AS .
CELL, 1991, 65 (07) :1281-1289
[16]   REGULATORY SUBUNITS OF CAMP-DEPENDENT PROTEIN-KINASES ARE DEGRADED AFTER CONJUGATION TO UBIQUITIN - A MOLECULAR MECHANISM UNDERLYING LONG-TERM SYNAPTIC PLASTICITY [J].
HEGDE, AN ;
GOLDBERG, AL ;
SCHWARTZ, JH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (16) :7436-7440
[17]  
JAFFRAY E, 1995, MOL CELL BIOL, V15, P2166
[18]  
KOPP EB, 1995, ADV IMMUNOL, V58, P2
[19]   DIFFERENTIAL EXPRESSION OF REL FAMILY MEMBERS IN HUMAN T-CELL LEUKEMIA-VIRUS TYPE I-INFECTED CELLS - TRANSCRIPTIONAL ACTIVATION OF C-REL BY TAX PROTEIN [J].
LI, CCH ;
RUSCETTI, FW ;
RICE, NR ;
CHEN, EY ;
YANG, NS ;
MIKOVITS, J ;
LONGO, DL .
JOURNAL OF VIROLOGY, 1993, 67 (07) :4205-4213
[20]   NF-KAPPA-B/REL FAMILY MEMBERS ARE PHYSICALLY ASSOCIATED PHOSPHOPROTEINS [J].
LI, CCH ;
KORNER, M ;
FERRIS, DK ;
CHEN, EY ;
DAI, RM ;
LONGO, DL .
BIOCHEMICAL JOURNAL, 1994, 303 :499-506