Siah Proteins: Novel Drug Targets in the Ras and Hypoxia Pathways

被引:72
作者
House, Colin M. [1 ]
Moeller, Andreas [1 ,2 ]
Bowtell, David D. L. [1 ,2 ]
机构
[1] Peter MacCallum Canc Ctr, Canc Genom & Genet Lab, Melbourne, Vic, Australia
[2] Univ Melbourne, Dept Biochem, Parkville, Vic 3052, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
UBIQUITIN LIGASE SIAH2; MURINE HOMOLOGS; GENE; P53; STABILITY; BINDING; IDENTIFICATION; TUMORIGENESIS; INHIBITION; HIPK2;
D O I
10.1158/0008-5472.CAN-09-1676
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The Siah (seven in absentia homolog) family of RING-domain proteins are components of ubiquitin ligase complexes, targeting proteins for proteasomal degradation. Siah family members have been reported to function in Ras, estrogen, DNA-damage, and hypoxia response pathways. Although earlier reports implicated Siah proteins as tumor suppressors, recent studies in mouse models have shown that Siah inhibition impairs tumor growth and metastasis. Given their central role in oncogenic and angiogenic pathways, Siah proteins are attractive novel therapeutic targets in cancer. [Cancer Res 2009;69(23):8835-8]
引用
收藏
页码:8835 / 8838
页数:4
相关论文
共 35 条
[1]   Effect of Disrupting Seven-in-Absentia Homolog 2 Function on Lung Cancer Cell Growth [J].
Ahmed, Atique U. ;
Schmidt, Rebecca L. ;
Park, Cheol Hong ;
Reed, Nanette R. ;
Hesse, Shayla E. ;
Thomas, Charles F. ;
Molina, Julian R. ;
Deschamps, Claude ;
Yang, Ping ;
Aubry, Marie C. ;
Tang, Amy H. .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2008, 100 (22) :1606-1629
[2]   Identification of innate immunity genes and pathways using a comparative genomics approach [J].
Alper, Scott ;
Laws, Rebecca ;
Lackford, Brad ;
Boyd, Windy A. ;
Dunlap, Paul ;
Freedman, Jonathan H. ;
Schwartz, David A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (19) :7016-7021
[3]   A role for Ebi in neuronal cell cycle control [J].
Boulton, SJ ;
Brook, A ;
Staehling-Hampton, K ;
Heitzler, P ;
Dyson, N .
EMBO JOURNAL, 2000, 19 (20) :5376-5386
[4]   An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response [J].
Calzado, Marco A. ;
de la Vega, Laureano ;
Moeller, Andreas ;
Bowtell, David D. L. ;
Schmitz, M. Lienhard .
NATURE CELL BIOLOGY, 2009, 11 (01) :85-U180
[5]   IDENTIFICATION OF GENES THAT INTERACT WITH THE SINA GENE IN DROSOPHILA EYE DEVELOPMENT [J].
CARTHEW, RW ;
NEUFELD, TP ;
RUBIN, GM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) :11689-11693
[6]   Gene expression - Emerging roles of ubiquitin in transcription regulation [J].
Conaway, RC ;
Brower, CS ;
Conaway, JW .
SCIENCE, 2002, 296 (5571) :1254-1258
[7]  
DELLA NG, 1993, DEVELOPMENT, V117, P1333
[8]   The ubiquitin ligase component Siah1a is required for completion of meiosis I in male mice [J].
Dickins, RA ;
Frew, IJ ;
House, CM ;
O'Bryan, MK ;
Holloway, AJ ;
Haviv, I ;
Traficante, N ;
de Kretser, DM ;
Bowtell, DDL .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (07) :2294-2303
[9]   Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes [J].
Frasor, J ;
Danes, JM ;
Funk, CC ;
Katzenellenbogen, BS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (37) :13153-13157
[10]   Generation and analysis of Siah2 mutant mice [J].
Frew, IJ ;
Hammond, VE ;
Dickins, RA ;
Quinn, JMW ;
Walkley, CR ;
Sims, NA ;
Schnall, R ;
Della, NG ;
Holloway, AJ ;
Digby, MR ;
Janes, PW ;
Tarlinton, DM ;
Purton, LE ;
Gillespie, MT ;
Bowtell, DDL .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (24) :9150-9161