Proteins of the Ras pathway as novel potential anticancer therapeutic targets

被引:5
作者
de Gunzburg, J [1 ]
机构
[1] Inst Curie, Sect Rech, INSERM, U528, F-75248 Paris 05, France
关键词
Ras; GTPase; oncogenesis; signal transduction; anticancer drugs;
D O I
10.1023/A:1007645631013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ras proteins are molecular switches that constitute a pivotal element in the control of cellular responses to many incoming signals, and in particular mitogenic stimulations. They act through multiple effector pathways that carry out the biological functions of Ras in cells. Since mutations that constitutively activate Ras proteins have been found in a high proportion of human malignancies and participate in oncogenesis, a number of therapeutic anticancer strategies aimed against the activity or action of Ras proteins have been developed. This paper reviews the principal aspects of the Ras signaling pathway and describes some of the attempts to develop antitumor drugs based on this concept.
引用
收藏
页码:345 / 358
页数:14
相关论文
共 156 条
[1]   GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN (GAP) INTERACTS WITH THE P21-RAS EFFECTOR BINDING DOMAIN [J].
ADARI, H ;
LOWY, DR ;
WILLUMSEN, BM ;
DER, CJ ;
MCCORMICK, F .
SCIENCE, 1988, 240 (4851) :518-520
[2]   Guanosine triphosphatase stimulation of oncogenic Ras mutants [J].
Ahmadian, MR ;
Zor, T ;
Vogt, D ;
Kabsch, W ;
Selinger, Z ;
Wittinghofer, A ;
Scheffzek, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :7065-7070
[3]   Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27(KIP1) [J].
Aktas, H ;
Cai, H ;
Cooper, GM .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (07) :3850-3857
[4]   CHARACTERIZATION OF A GUANINE-NUCLEOTIDE DISSOCIATION STIMULATOR FOR A RAS-RELATED GTPASE [J].
ALBRIGHT, CF ;
GIDDINGS, BW ;
LIU, J ;
VITO, M ;
WEINBERG, RA .
EMBO JOURNAL, 1993, 12 (01) :339-347
[5]   RAS GENES [J].
BARBACID, M .
ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :779-827
[6]   In vitro inhibition of Ras-Raf association by short peptides [J].
Barnard, D ;
Sun, HY ;
Baker, L ;
Marshall, MS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 247 (01) :176-180
[7]   A farnesyltransferase inhibitor induces tumor regression in transgenic mice harboring multiple oncogenic mutations by mediating alterations in both cell cycle control and apoptosis [J].
Barrington, RE ;
Subler, MA ;
Rands, E ;
Omer, CA ;
Miller, PJ ;
Hundley, JE ;
Koester, SK ;
Troyer, DA ;
Bearss, DJ ;
Conner, MW ;
Gibbs, JB ;
Hamilton, K ;
Koblan, KS ;
Mosser, SD ;
O'Neill, TJ ;
Schaber, MD ;
Senderak, ET ;
Windle, JJ ;
Oliff, A ;
Kohl, NE .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (01) :85-92
[8]   p14ARF links the tumour suppressors RB and p53 [J].
Bates, S ;
Phillips, AC ;
Clark, PA ;
Stott, F ;
Peters, G ;
Ludwig, RL ;
Vousden, KH .
NATURE, 1998, 395 (6698) :124-125
[9]   THE EFFECTOR DOMAIN OF RAB6, PLUS A HIGHLY HYDROPHOBIC-C TERMINUS, IS REQUIRED FOR GOLGI-APPARATUS LOCALIZATION [J].
BERANGER, F ;
PATERSON, H ;
POWERS, S ;
DEGUNZBURG, J ;
HANCOCK, JF .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (01) :744-758
[10]   PROTEINS REGULATING RAS AND ITS RELATIVES [J].
BOGUSKI, MS ;
MCCORMICK, F .
NATURE, 1993, 366 (6456) :643-654