Targeting translation for treatment of cancer -: A novel role for IRIES?

被引：41

作者：

Holcík, M ^{[1
]}

机构：

[1] Childrens Hosp Eastern Ontario, Apoptosis Res Ctr, Inst Res, Ottawa, ON K1H 8L1, Canada

来源：

CURRENT CANCER DRUG TARGETS | 2004年 / 4卷 / 03期

关键词：

D O I：

10.2174/1568009043333005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Protein synthesis plays an important role in the regulation of cell proliferation. While the role of cap-dependent translation in cell transformation has been studied extensively another translation initiation mechanism, internal initiation of cellular mRNAs, emerged recently and is relatively unappreciated and poorly understood. Internal initiation is mediated by IRES elements that are found in the 5' untranslated region (5' UTR) of mRNA. Curiously, several oncogenes, growth factors and proteins involved in the regulation of programmed cell death contain IRES elements in their 5' UTRs. Internal initiation escapes many control mechanisms that regulate cap-dependent translation. In this review I will discuss the data supporting the hypothesis that selective translation of these factors may contribute to the survival of cancer cells under stressful situations, such as lack of nutrients, hypoxia, or therapy-induced DNA damage and contributes to the development and progression of cancer and to the establishment of cancer cells that are resistant to conventional therapies.

引用

页码：299 / 311

页数：13

共 162 条

[1] Apoptosomes: engines for caspase activation [J].

Adams, JM ;

Cory, S .

CURRENT OPINION IN CELL BIOLOGY, 2002, 14 (06) :715-720

[2] Hypoxia-induced VEGF enhances tumor survivability via suppression of serum deprivation-induced apoptosis [J].

Baek, JH ;

Jang, JE ;

Kang, CM ;

Chung, HY ;

Kim, ND ;

Kim, KW .

ONCOGENE, 2000, 19 (40) :4621-4631

[3] Alternative initiation of translation accounts for a 67/45 kDa dimorphism of the human estrogen receptor ERα [J].

Barraille, P ;

Chinestra, P ;

Bayard, F ;

Faye, JC .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 257 (01) :84-88

[4] The influence of the cell cycle, differentiation and irradiation on the nuclear location of the abl, bcr and c-myc genes in human leukemic cells [J].

Bártová, E ;

Kozubek, S ;

Kozubek, M ;

Jirsová, P ;

Lukásová, E ;

Skalnícová, M ;

Buchnicková, K .

LEUKEMIA RESEARCH, 2000, 24 (03) :233-241

[5]

Berkel HJ, 2001, CANCER EPIDEM BIOMAR, V10, P663

[6] THE TRANSLATIONAL REPRESSION MEDIATED BY THE PLATELET-DERIVED GROWTH-FACTOR 2/C-SIS MESSENGER-RNA LEADER IS RELIEVED DURING MEGAKARYOCYTIC DIFFERENTIATION [J].

BERNSTEIN, J ;

SHEFLER, I ;

ELROYSTEIN, O .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (18) :10559-10565

[7]

Bernstein J, 1997, J BIOL CHEM, V272, P9356

[8] BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release [J].

Bimston, D ;

Song, JH ;

Winchester, D ;

Takayama, S ;

Reed, JC ;

Morimoto, RI .

EMBO JOURNAL, 1998, 17 (23) :6871-6878

[9]

BONNEAU AM, 1987, J BIOL CHEM, V262, P11134

[10] Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma [J].

Brass, N ;

Heckel, D ;

Sahin, U ;

Pfreundschuh, M ;

Sybrecht, GW ;

Meese, E .

HUMAN MOLECULAR GENETICS, 1997, 6 (01) :33-39

← 1 2 3 4 5 6 7 8 9 10 →