Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: Transforming ability and frequent detection in human cancer

被引:257
作者
Sigalas, I
Calvert, AH
Anderson, JJ
Neal, DE
Lunec, J
机构
[1] UNIV NEWCASTLE UPON TYNE,SCH MED,CANC RES UNIT,NEWCASTLE TYNE NE2 4HH,TYNE & WEAR,ENGLAND
[2] UNIV NEWCASTLE UPON TYNE,SCH MED,DEPT PATHOL,NEWCASTLE TYNE NE2 4HH,TYNE & WEAR,ENGLAND
[3] UNIV NEWCASTLE UPON TYNE,SCH MED,DEPT SURG,NEWCASTLE TYNE NE2 4HH,TYNE & WEAR,ENGLAND
关键词
D O I
10.1038/nm0896-912
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 mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave foci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.
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收藏
页码:912 / 917
页数:6
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