Dual specificity protein phosphatases: Therapeutic targets for cancer and Alzheimer's disease

被引:78
作者
Ducruet, AP [1 ]
Vogt, A
Wipf, P
Lazo, JS
机构
[1] Univ Pittsburgh, Inst Canc, Dept Pharmacol, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Inst Canc, Combinatorial Chem Ctr, Pittsburgh, PA 15261 USA
[3] Univ Pittsburgh, Inst Canc, Fiske Drug Discovery Lab, Pittsburgh, PA 15261 USA
[4] Univ Pittsburgh, Inst Canc, Dept Chem, Pittsburgh, PA 15261 USA
关键词
Cdc25; Cdk; MKP; MAPK; drug discovery;
D O I
10.1146/annurev.pharmtox.45.120403.100040
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The complete sequencing of the human genome is generating many novel targets for drug discovery. Understanding the pathophysiological roles of these putative targets and assessing their suitability for therapeutic intervention has become the major hurdle for drug discovery efforts. The dual-specificity phosphatases (DSPases), which dephosphorylate serine, threonine, and tyrosine residues in the same protein substrate, have important roles in multiple signaling pathways and appear to be deregulated in cancer and Alzheimer's disease. We examine the potential of DSPases as new molecular therapeutic targets for the treatment of human disease.
引用
收藏
页码:725 / 750
页数:26
相关论文
共 156 条
[1]   Protein tyrosine phosphatases in the human genome [J].
Alonso, A ;
Sasin, J ;
Bottini, N ;
Friedberg, I ;
Friedberg, I ;
Osterman, A ;
Godzik, A ;
Hunter, T ;
Dixon, J ;
Mustelin, T .
CELL, 2004, 117 (06) :699-711
[2]  
Aref S, 2003, Hematology, V8, P183, DOI 10.1080/1024533031000090829
[3]   Phosphorylation of human CDC25B phosphatase by CDK1-cyclin A triggers its proteasome-dependent degradation [J].
Baldin, V ;
Cans, C ;
Knibiehler, M ;
Ducommun, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (52) :32731-32734
[4]   Increased MAPK activity and MKP-1 overexpression in human gastric adenocarcinoma [J].
Bang, YJ ;
Kwon, JH ;
Kang, SH ;
Kim, JW ;
Yang, YC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 250 (01) :43-47
[5]   Mammalian G1- and S-phase checkpoints in response to DNA damage [J].
Bartek, J ;
Lukas, J .
CURRENT OPINION IN CELL BIOLOGY, 2001, 13 (06) :738-747
[6]   Design and synthesis of macrocyclic inhibitors of phosphatase Cdc25B [J].
Bäurle, S ;
Blume, T ;
Günther, J ;
Henschel, D ;
Hillig, RC ;
Husemann, M ;
Mengel, A ;
Parchmann, C ;
Schmid, E ;
Skuballa, W .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (07) :1673-1677
[7]   3 TUMOR-SUPPRESSOR REGIONS ON CHROMOSOME-11P IDENTIFIED BY HIGH-RESOLUTION DELETION MAPPING IN HUMAN NON-SMALL-CELL LUNG-CANCER [J].
BEPLER, G ;
GARCIABLANCO, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (12) :5513-5517
[8]   Brain genomic response following hypoxia and re-oxygenation in the neonatal rat - Identification of genes that might contribute to hypoxia-induced ischemic tolerance [J].
Bernaudin, M ;
Tang, Y ;
Reilly, M ;
Petit, E ;
Sharp, FR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) :39728-39738
[9]  
Blomberg I, 1999, MOL CELL BIOL, V19, P6183
[10]   Novel synthetic inhibitor of CDC25 phosphatases:: BN82002 [J].
Brezak, MC ;
Quaranta, M ;
Mondésert, O ;
Galcera, MO ;
Lavergne, O ;
Alby, F ;
Cazales, M ;
Baldin, W ;
Thurieau, C ;
Harnett, J ;
Lanco, C ;
Kasprzyk, PG ;
Prevost, GP ;
Ducommun, B .
CANCER RESEARCH, 2004, 64 (09) :3320-3325