The Multifaceted Roles of USP7: New Therapeutic Opportunities

被引:216
作者
Nicholson, Benjamin [1 ]
Kumar, K. G. Suresh [1 ]
机构
[1] Progenra Inc, Malvern, PA 19355 USA
关键词
USP7; HAUSP; Deubiquitylase; Cancer; Ubiquitin; HERPES-SIMPLEX-VIRUS; UBIQUITIN-SPECIFIC PROTEASE; DNA-DAMAGE-RESPONSE; BETA-TRCP; GMP SYNTHETASE; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; CHECKPOINT; ICP0; CELL;
D O I
10.1007/s12013-011-9185-5
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
The deubiquitylating enzyme USP7 (HAUSP) sits at a critical node regulating the activities of numerous proteins broadly characterized as tumor suppressors, DNA repair proteins, immune responders, viral proteins, and epigenetic modulators. Aberrant USP7 activity may promote oncogenesis and viral disease making it a compelling target for therapeutic intervention. Disclosed drug discovery programs have identified inhibitors of USP7 such as P005091 with cellular proof of concept and anti-proliferative activity in cancer models. Taken together, USP7 inhibitors hold promise as a new strategy for the treatment of disease.
引用
收藏
页码:61 / 68
页数:8
相关论文
共 82 条
[1]   DNA damage checkpoints: from initiation to recovery or adaptation [J].
Bartek, Jiri ;
Lukas, Jiri .
CURRENT OPINION IN CELL BIOLOGY, 2007, 19 (02) :238-245
[2]   The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint [J].
Bassermann, Florian ;
Frescas, David ;
Guardavaccaro, Daniele ;
Busino, Luca ;
Peschiaroli, Angelo ;
Pagano, Michele .
CELL, 2008, 134 (02) :256-267
[3]   GUANOSINE-5'-PHOSPHATE SYNTHETASE AND GUANOSINE-5'-PHOSPHATE KINASE IN RAT HEPATOMAS AND KIDNEY TUMORS [J].
BORITZKI, TJ ;
JACKSON, RC ;
MORRIS, HP ;
WEBER, G .
BIOCHIMICA ET BIOPHYSICA ACTA, 1981, 658 (01) :102-110
[4]   The herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 interacts with and ubiquitinates p53 [J].
Boutell, C ;
Everett, RD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (38) :36596-36602
[5]   Mdm2 Induces Mono-Ubiquitination of FOXO4 [J].
Brenkman, Arjan B. ;
de Keizer, Peter L. J. ;
van den Broek, Niels J. F. ;
Jochemsen, A. G. ;
Burgering, Boudewijn M. Th. .
PLOS ONE, 2008, 3 (07)
[6]   The peptidyl-isomerase Pin1 regulates p27kip1 expression through inhibition of Forkhead box O tumor suppressors [J].
Brenkman, Arjan B. ;
de Keizer, Peter L. J. ;
van den Broek, Niels J. F. ;
van der Groep, Petra ;
van Diest, Paul J. ;
van der Horst, Armando ;
Smits, Alida M. M. ;
Burgering, Boudewijn M. T. .
CANCER RESEARCH, 2008, 68 (18) :7597-7605
[7]   Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage [J].
Busino, L ;
Donzelli, M ;
Chiesa, M ;
Guardavaccaro, D ;
Ganoth, D ;
Dorrello, NV ;
Hershko, A ;
Pagano, M ;
Draetta, GF .
NATURE, 2003, 426 (6962) :87-91
[8]  
CAO P, 2010, Patent No. 2010029358
[9]   Herpes Simplex Virus ICP0 Promotes both Histone Removal and Acetylation on Viral DNA during Lytic Infection [J].
Cliffe, Anna R. ;
Knipe, David M. .
JOURNAL OF VIROLOGY, 2008, 82 (24) :12030-12038
[10]   Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells [J].
Colland, Frederic ;
Formstecher, Etienne ;
Jacq, Xavier ;
Reverdy, Celine ;
Planquette, Cecile ;
Conrath, Susan ;
Trouplin, Virginie ;
Bianchi, Julie ;
Aushev, Vasily N. ;
Camonis, Jacques ;
Calabrese, Alessandra ;
Borg-Capra, Catherine ;
Sippl, Wolfgang ;
Collura, Vincent ;
Boissy, Guillaume ;
Rain, Jean-Christophe ;
Guedat, Philippe ;
Delansorne, Remi ;
Daviet, Laurent .
MOLECULAR CANCER THERAPEUTICS, 2009, 8 (08) :2286-2295