Nuclear transport as a target for cell growth

被引：62

作者：

Kau, TR ^{[1
]}

Silver, PA

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

来源：

DRUG DISCOVERY TODAY | 2003年 / 8卷 / 02期

关键词：

D O I：

10.1016/S1359-6446(02)02562-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor kappaB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a potential therapeutic target, only two nuclear transport inhibitors have been reported. Here, we explore the roles of small-molecule inhibitors that cause target proteins to sequester in either the nucleus or cytoplasm. Methods of artificially targeting proteins to the nucleus or cytoplasm using peptide aptamer technology are also discussed.

引用

页码：78 / 85

页数：8

共 74 条

[1] HIGHER-ORDER CHROMOSOME STRUCTURE IS AFFECTED BY COLD-SENSITIVE MUTATIONS IN A SCHIZOSACCHAROMYCES-POMBE GENE CRM1+ WHICH ENCODES A 115-KD PROTEIN PREFERENTIALLY LOCALIZED IN THE NUCLEUS AND AT ITS PERIPHERY [J].

ADACHI, Y ;

YANAGIDA, M .

JOURNAL OF CELL BIOLOGY, 1989, 108 (04) :1195-1207

[2] Role of translocation in the activation and function of protein kinase B [J].

Andjelkovic, M ;

Alessi, DR ;

Meier, R ;

Fernandez, A ;

Lamb, NJC ;

Frech, M ;

Cron, P ;

Cohen, P ;

Lucocq, JM ;

Hemmings, BA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (50) :31515-31524

[3] Inhibition of tumor necrosis factor-α-induced nuclear translocation and activation of NF-κB by dehydroxymethylepoxyquinomicin [J].

Ariga, A ;

Namekawa, J ;

Matsumoto, N ;

Inoue, J ;

Umezawa, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (27) :24625-24630

[4] An essential role for NF-kappa B in preventing TNF-alpha-induced cell death [J].

Beg, AA ;

Baltimore, D .

SCIENCE, 1996, 274 (5288) :782-784

[5] I-KAPPA-B INTERACTS WITH THE NUCLEAR-LOCALIZATION SEQUENCES OF THE SUBUNITS OF NF-KAPPA-B - A MECHANISM FOR CYTOPLASMIC RETENTION [J].

BEG, AA ;

RUBEN, SM ;

SCHEINMAN, RI ;

HASKILL, S ;

ROSEN, CA ;

BALDWIN, AS .

GENES & DEVELOPMENT, 1992, 6 (10) :1899-1913

[6] Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 [J].

Biggs, WH ;

Meisenhelder, J ;

Hunter, T ;

Cavenee, WK ;

Arden, KC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7421-7426

[7] An intact HDM2 RING-finger domain is required for nuclear exclusion of p53 [J].

Boyd, SD ;

Tsai, KY ;

Jacks, T .

NATURE CELL BIOLOGY, 2000, 2 (09) :563-568

[8] Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX [J].

Brownawell, AM ;

Kops, GJPL ;

Macara, IG ;

Burgering, BMT .

MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (10) :3534-3546

[9] 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport [J].

Brunet, A ;

Kanai, F ;

Stehn, J ;

Xu, J ;

Sarbassova, D ;

Frangioni, JV ;

Dalal, SN ;

DeCaprio, JA ;

Greenberg, ME ;

Yaffe, MB .

JOURNAL OF CELL BIOLOGY, 2002, 156 (05) :817-828

[10] Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a) [J].

Brunet, A ;

Park, J ;

Tran, H ;

Hu, LS ;

Hemmings, BA ;

Greenberg, ME .

MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (03) :952-965

← 1 2 3 4 5 6 7 8 →