Complementation cloning of NEMO, a component of the IκB kinase complex essential for NF-κB activation

被引：929
作者：
Yamaoka, S
Courtois, G
Bessia, C
Whiteside, ST
Weil, R
Agou, F
Kirk, HE
Kay, RJ
Israël, A
机构：
[1] Inst Pasteur, Unite Biol Mol Express Gen, CNRS, URA 1773, F-75724 Paris 15, France
[2] Inst Pasteur, Unite Regulat Enzymat Act Cellulaires, CNRS, URA 1773, F-75724 Paris, France
[3] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 4E6, Canada
[4] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 606, Japan
来源：
CELL | 1998年 / 93卷 / 07期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1016/S0092-8674(00)81466-X
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：
We have characterized a flat cellular variant of HTLV-1 Tax-transformed rat fibroblasts, 5R, which is unresponsive to all tested NF-kappa B activating stimuli, and we report here its genetic complementation. The recovered full-length cDNA encodes a 48 kDa protein, NEMO (NF-kappa B Essential MOdulator), which contains a putative leucine zipper motif. This protein is absent from 5R cells, is part of the high molecular weight I kappa B kinase complex, and is required for its formation. In vitro, NEMO can homodimerize and directly interacts with IKK-2. The NEMO cDNA was also able to complement another NF-kappa B-unresponsive cell line, 1.3E2, in which the protein is also absent, allowing us to demonstrate that this factor is required not only for Tax but also for LPS, PMA, and IL-1 stimulation of NF-kappa B activity.
引用
收藏
页码：1231 / 1240
页数：10
相关论文
共 28 条
[1]   SUPPRESSION OF HUMAN COLORECTAL-CARCINOMA CELL-GROWTH BY WILD-TYPE-P53 [J].
BAKER, SJ ;
MARKOWITZ, S ;
FEARON, ER ;
WILLSON, JKV ;
VOGELSTEIN, B .
SCIENCE, 1990, 249 (4971) :912-915
[2]   The NF-kappa B and I kappa B proteins: New discoveries and insights [J].
Baldwin, AS .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :649-683
[3]   Site-specific phosphorylation of I kappa B alpha by a novel ubiquitination-dependent protein kinase activity [J].
Chen, ZJ ;
Parent, L ;
Maniatis, T .
CELL, 1996, 84 (06) :853-862
[4]   Characterization of a mutant cell line that does not activate NF-kappa B in response to multiple stimuli [J].
Courtois, G ;
Whiteside, ST ;
Sibley, CH ;
Israel, A .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (03) :1441-1449
[5]   JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].
DARNELL, JE ;
KERR, IM ;
STARK, GR .
SCIENCE, 1994, 264 (5164) :1415-1421
[6]   A cytokine-responsive I kappa B kinase that activates the transcription factor NF-kappa B [J].
DiDonato, JA ;
Hayakawa, M ;
Rothwarf, DM ;
Zandi, E ;
Karin, M .
NATURE, 1997, 388 (6642) :548-554
[7]   SINGLE CELL ASSAY OF A TRANSCRIPTION FACTOR REVEALS A THRESHOLD IN TRANSCRIPTION ACTIVATED BY SIGNALS EMANATING FROM THE T-CELL ANTIGEN RECEPTOR [J].
FIERING, S ;
NORTHROP, JP ;
NOLAN, GP ;
MATTILA, PS ;
CRABTREE, GR ;
HERZENBERG, LA .
GENES & DEVELOPMENT, 1990, 4 (10) :1823-1834
[8]   BLASTICIDIN S-RESISTANCE GENE (BSR) - A NOVEL SELECTABLE MARKER FOR MAMMALIAN-CELLS [J].
IZUMI, M ;
MIYAZAWA, H ;
KAMAKURA, T ;
YAMAGUCHI, I ;
ENDO, T ;
HANAOKA, F .
EXPERIMENTAL CELL RESEARCH, 1991, 197 (02) :229-233
[9]   THE DNA-BINDING SUBUNIT OF NF-KAPPA-B IS IDENTICAL TO FACTOR KBF1 AND HOMOLOGOUS TO THE REL ONCOGENE PRODUCT [J].
KIERAN, M ;
BLANK, V ;
LOGEAT, F ;
VANDEKERCKHOVE, J ;
LOTTSPEICH, F ;
LEBAIL, O ;
URBAN, MB ;
KOURILSKY, P ;
BAEUERLE, PA ;
ISRAEL, A .
CELL, 1990, 62 (05) :1007-1018
[10]   ABLATION OF TRANSPLANTED HTLV-I TAX-TRANSFORMED TUMORS IN MICE BY ANTISENSE INHIBITION OF NF-KAPPA-B [J].
KITAJIMA, I ;
SHINOHARA, T ;
BILAKOVICS, J ;
BROWN, DA ;
XU, X ;
NERENBERG, M .
SCIENCE, 1992, 258 (5089) :1792-1795
123