EWS-ETS oncoproteins: The linchpins of Ewing tumors

被引:126
作者
Janknecht, R [1 ]
机构
[1] Mayo Clin Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
关键词
cancer; Ewing's sarcoma protein; FUS; gene transcription; RNA splicing;
D O I
10.1016/j.gene.2005.08.007
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Ewing tumors, which comprise Ewing's sarcoma and peripheral primitive neuroectodermal tumors, are highly aggressive and mostly affect children and adolescents. Their molecular signature is a chromosomal translocation leading to the generation of EWS-ETS (or very rarely FUS-ETS) fusion proteins that are capable of transforming cells. These oncoproteins act as aberrant transcription factors due to the fusion of an ETS DNA binding domain to a highly potent EWS (or FUS) transactivation domain. Accordingly, many EWS-ETS target genes have been identified whose dysregulation could contribute to the development of tumor formation. Furthermore, EWS-ETS oncoproteins may impact on RNA splicing or affect other proteins through disturbing their ability to form functional complexes. The molecular knowledge gained so far from studying EWS-ETS oncoproteins has not only broadened our understanding of Ewing tumors but also improved the diagnosis of these highly undifferentiated tumors. In addition, several potential prognostic markers have been uncovered and novel therapies are suggested that may improve the still dismal survival rate of Ewing tumor patients. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 14
页数:14
相关论文
共 236 条
[121]  
MAO XH, 1994, J BIOL CHEM, V269, P18216
[122]  
Martini A, 2002, CANCER RES, V62, P5408
[123]   TGF-β signal transduction [J].
Massagué, J .
ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :753-791
[124]   A novel zinc finger gene is fused to EWS in small round cell tumor [J].
Mastrangelo, T ;
Modena, P ;
Tornielli, S ;
Bullrich, F ;
Testi, MA ;
Mezzelani, A ;
Radice, P ;
Azzarelli, A ;
Pilotti, S ;
Croce, CM ;
Pierotti, MA ;
Sozzi, G .
ONCOGENE, 2000, 19 (33) :3799-3804
[125]   Rapamycin induces the fusion-type independent downregulation of the EWS/FLI-1 proteins and inhibits Ewing's sarcoma cell proliferation [J].
Mateo-Lozano, S ;
Tirado, OM ;
Notario, V .
ONCOGENE, 2003, 22 (58) :9282-9287
[126]   Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G1 regulatory genes [J].
Matsumoto, Y ;
Tanaka, K ;
Nakatani, F ;
Matsunobu, T ;
Matsuda, S ;
Iwamoto, Y .
BRITISH JOURNAL OF CANCER, 2001, 84 (06) :768-775
[127]   The prognostic and therapeutic relevance of p27kip1 in Ewing's family tumors [J].
Matsunobu, T ;
Tanaka, K ;
Matsumoto, Y ;
Nakatani, F ;
Sakimura, R ;
Hanada, M ;
Li, X ;
Oda, Y ;
Naruse, I ;
Hoshino, H ;
Tsuneyoshi, M ;
Miura, H ;
Iwamoto, Y .
CLINICAL CANCER RESEARCH, 2004, 10 (03) :1003-1012
[128]   FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain [J].
Maurer, P ;
T'Sas, F ;
Coutte, L ;
Callens, N ;
Brenner, C ;
Van Lint, C ;
de Launoit, Y ;
Baert, JL .
ONCOGENE, 2003, 22 (21) :3319-3329
[129]   THE EWINGS-SARCOMA EWS/FLI-1 FUSION GENE ENCODES A MORE POTENT TRANSCRIPTIONAL ACTIVATOR AND IS A MORE POWERFUL TRANSFORMING GENE THAN FLI-1 [J].
MAY, WA ;
LESSNICK, SL ;
BRAUN, BS ;
KLEMSZ, M ;
LEWIS, BC ;
LUNSFORD, LB ;
HROMAS, R ;
DENNY, CT .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (12) :7393-7398
[130]   EWING SARCOMA 11-22 TRANSLOCATION PRODUCES A CHIMERIC TRANSCRIPTION FACTOR THAT REQUIRES THE DNA-BINDING DOMAIN ENCODED BY FLI1 FOR TRANSFORMATION [J].
MAY, WA ;
GISHIZKY, ML ;
LESSNICK, SL ;
LUNSFORD, LB ;
LEWIS, BC ;
DELATTRE, O ;
ZUCMAN, J ;
THOMAS, G ;
DENNY, CT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (12) :5752-5756