Cap in hand Targeting eIF4E

被引:52
作者
Fischer, Peter M. [1 ,2 ]
机构
[1] Univ Nottingham, Ctr Biomol Sci, Nottingham NG7 2RD, England
[2] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England
关键词
cancer; translation; eIF4E; ribavirin; mRNA cap; drug discovery; drug target; MESSENGER-RNA CAP; INITIATION-FACTOR; 4E; CATION-PI INTERACTIONS; TRANSLATION INITIATION; BINDING PROTEIN; DEPENDENT TRANSLATION; EUKARYOTIC TRANSLATION; STRUCTURAL BASIS; CANCER-THERAPY; EIF4E-FAMILY MEMBERS;
D O I
10.4161/cc.8.16.9301
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recognition of the mRNA cap structure by the translation initiation factor eIF4E is central to protein synthesis in general and eIF4E activity is especially important for the production of many of the proteins that give rise to the hallmarks of cancer. Because transformed cells have a heightened requirement for the expression of prosurvival factors, targeting translation appears to be an attractive anticancer strategy and proof-of-concept studies in which oncogenic eIF4E function is suppressed in various different ways show that tumour cells are selectively sensitive to inhibition of protein synthesis at the level of eIF4E. The emerging understanding of the functions, regulation, and structural biology of eIF4E now makes possible the pharmacological targeting of this key translation initiation factor.
引用
收藏
页码:2535 / 2541
页数:7
相关论文
共 80 条
[1]  
ADAMS BL, 1978, J BIOL CHEM, V253, P2589
[2]  
ASSOULINE S, 2009, BLOOD
[3]   Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells [J].
Avdulov, S ;
Li, S ;
Michalek, V ;
Burrichter, D ;
Peterson, M ;
Perlman, DM ;
Manivel, JC ;
Sonenberg, N ;
Yee, D ;
Bitterman, PB ;
Polunovsky, VA .
CANCER CELL, 2004, 5 (06) :553-563
[4]   Lost in translation: Dysregulation of cap-dependent translation and cancer [J].
Bjornsti, MA ;
Houghton, PJ .
CANCER CELL, 2004, 5 (06) :519-523
[5]   Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A [J].
Bordeleau, ME ;
Mori, A ;
Oberer, M ;
Lindqvist, L ;
Chard, LS ;
Higa, T ;
Belsham, GJ ;
Wagner, G ;
Tanaka, J ;
Pelletier, J .
NATURE CHEMICAL BIOLOGY, 2006, 2 (04) :213-220
[6]   PI3K and mTOR inhibitors - a new generation of targeted anticancer agents [J].
Brachmann, Saskia ;
Fritsch, Christine ;
Maira, Saveur-Michel ;
Garcia-Echeverria, Carlos .
CURRENT OPINION IN CELL BIOLOGY, 2009, 21 (02) :194-198
[7]   Crystallographic and mass spectrometric characterisation of elF4E with N7-alkylated cap derivatives [J].
Brown, Christopher J. ;
McNae, Iain ;
Fischer, Peter M. ;
Walkinshaw, Malcolm D. .
JOURNAL OF MOLECULAR BIOLOGY, 2007, 372 (01) :7-15
[8]   Crystallization of eIF4E complexed with eIF4GI peptide and glycerol reveals distinct structural differences around the cap-binding site [J].
Brown, Christopher J. ;
Verma, Chandra S. ;
Walkinshaw, Malcolm D. ;
Lane, David P. .
CELL CYCLE, 2009, 8 (12) :1905-1911
[9]   Quantitative assessment of mRNA cap analogues as inhibitors of in vitro translation [J].
Cai, A ;
Jankowska-Anyszka, M ;
Centers, A ;
Chlebicka, L ;
Stepinski, J ;
Stolarski, R ;
Darzynkiewicz, E ;
Rhoads, RE .
BIOCHEMISTRY, 1999, 38 (26) :8538-8547
[10]   A SPECTROSCOPIC STUDY OF THE BINDING OF N-7-SUBSTITUTED CAP ANALOGS TO HUMAN PROTEIN-SYNTHESIS INITIATION FACTOR-4E [J].
CARBERRY, SE ;
DARZYNKIEWICZ, E ;
STEPINSKI, J ;
TAHARA, SM ;
RHOADS, RE ;
GOSS, DJ .
BIOCHEMISTRY, 1990, 29 (13) :3337-3341