LOSS OF THE AMINO-TERMINAL HELIX-LOOP-HELIX DOMAIN OF THE VAV PROTOONCOGENE ACTIVATES ITS TRANSFORMING POTENTIAL

被引：166

作者：

KATZAV, S ^{[1
]}

CLEVELAND, JL ^{[1
]}

HESLOP, HE ^{[1
]}

PULIDO, D ^{[1
]}

机构：

[1] NCI, FREDERICK CANC RES FACIL, BRI BASIC RES PROGRAM, FREDERICK, MD 21701 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 1991年 / 11卷 / 04期

关键词：

D O I：

10.1128/MCB.11.4.1912

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：

vav, a novel human oncogene, was originally generated in vitro by replacement of its normal 5' coding sequences with sequences from pSV2neo DNA, cotransfected as a selectable marker (S. Katzav, D. Martin-Zanca, and M. Barbacid, EMBO J. 8:2283-2290, 1989). The vav proto-oncogene is normally expressed in cells of hematopoietic origin. To determine whether the 5' rearrangement of vav or its ectopic expression in NIH 3T3 cells contributes to its transforming potential, we isolated murine and human proto-vav cDNA clones as well as human genomic clones corresponding to the 5' end of the gene. Normal proto-vav was poorly transforming in NIH 3T3 cells, whereas truncation of its 5' end greatly enhanced its transforming activity. The relative failure of full-length proto-vav cDNA clones to transform NIH 3T3 cells indicates that the transforming activity of vav is not simply due to ectopic expression. Analysis of the predicted amino terminus of the vav proto-oncogene shows that it contains a helix-loop-helix domain and a leucine zipper motif similar to that of myc family proteins, though it lacks a basic region that is usually found adjacent to helix-loop-helix domains. Loss of the helix-loop-helix domain of proto-vav, either by truncation or by rearrangement with pSV2neo sequences, activates its oncogenic potential.

引用

页码：1912 / 1920

页数：9

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