The many faces of β-TrCP E3 ubiquitin ligases:: reflections in the magic mirror of cancer

被引:277
作者
Fuchs, SY
Spiegelman, VS
Kumar, KGS
机构
[1] Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA
[2] AMC, Canc Res Ctr, Lakewood, CO 80214 USA
关键词
beta-TrCP; F-box; ubiquitin ligase; NF-kappa B; beta-catenin;
D O I
10.1038/sj.onc.1207389
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
Beta-transducin repeats-containing proteins (beta-TrCP) serve as the substrate recognition subunits for the SCFbeta-TrCP E3 ubiquitin ligases. These ligases ubiquitinate specifically phosphorylated substrates and play a pivotal role in the regulation of cell division and various signal transduction pathways, which, in turn, are essential for many aspects of tumorigenesis. We review the functions of the SCFbeta-TrCP ligases in the light of their relevance to cell growth, survival and transformation. Mechanisms underlying beta-TrCP regulation and their aberration in human and animal cancer as well as prospective of targeting beta-TrCP as a means of anticancer therapy are also discussed.
引用
收藏
页码:2028 / 2036
页数:9
相关论文
共 97 条
[91]   The SCF ubiquitin ligase protein Slimb regulates centrosome duplication in Drosophila [J].
Wojcik, EJ ;
Glover, DM ;
Hays, TS .
CURRENT BIOLOGY, 2000, 10 (18) :1131-1134
[92]   β-TrCP mediates the signal-induced ubiquitination of IκBβ [J].
Wu, C ;
Ghosh, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (42) :29591-29594
[93]   Structure of a β-TrCP1-Skp1-β-catenin complex:: Destruction motif binding and lysine specificity of the SCFβ-TrCP1 ubiquitin ligase [J].
Wu, G ;
Xu, GZ ;
Schulman, BA ;
Jeffrey, PD ;
Harper, JW ;
Pavletich, NP .
MOLECULAR CELL, 2003, 11 (06) :1445-1456
[94]   Inhibition of NF-kappa B cellular function via specific targeting of the I kappa B-ubiquitin ligase [J].
Yaron, A ;
Gonen, H ;
Alkalay, I ;
Hatzubai, A ;
Jung, S ;
Beyth, S ;
Mercurio, F ;
Manning, AM ;
Ciechanover, A ;
Ben-Neriah, Y .
EMBO JOURNAL, 1997, 16 (21) :6486-6494
[95]   Identification of the receptor component of the IκBα-ubiquitin ligase [J].
Yaron, A ;
Hatzubai, A ;
Davis, M ;
Lavon, I ;
Amit, S ;
Manning, AM ;
Andersen, JS ;
Mann, M ;
Mercurio, F ;
Ben-Neriah, Y .
NATURE, 1998, 396 (6711) :590-594
[96]   Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex [J].
Zheng, N ;
Schulman, BA ;
Song, LZ ;
Miller, JJ ;
Jeffrey, PD ;
Wang, P ;
Chu, C ;
Koepp, DM ;
Elledge, SJ ;
Pagano, M ;
Conaway, RC ;
Conaway, JW ;
Harper, JW ;
Pavletich, NP .
NATURE, 2002, 416 (6882) :703-709
[97]   Harnessing the ubiquitination machinery to target the degradation of specific cellular proteins [J].
Zhou, PB ;
Bogacki, R ;
McReynolds, L ;
Howley, PM .
MOLECULAR CELL, 2000, 6 (03) :751-756