ONCOGENIC ACTIVITY OF THE C-MYC PROTEIN REQUIRES DIMERIZATION WITH MAX

被引：507

作者：

AMATI, B ^{[1
]}

BROOKS, MW ^{[1
]}

LEVY, N ^{[1
]}

LITTLEWOOD, TD ^{[1
]}

EVAN, GI ^{[1
]}

LAND, H ^{[1
]}

机构：

[1] IMPERIAL CANC RES FUND, BIOCHEM CELL NUCLEUS LAB, LONDON WC2A 3PX, ENGLAND

来源：

CELL | 1993年 / 72卷 / 02期

关键词：

D O I：

10.1016/0092-8674(93)90663-B

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：

c-Myc (Myc) and Max proteins dimerize and bind DNA through basic-helix-loop-helix-leucine zipper motifs (b-HLH-LZ). Using a genetic approach, we demonstrate that binding to Max is essential for Myc transforming activity and that Myc homodimers are inactive. Mutants of Myc and Max that bind efficiently to each other but not to their wild-type partners were generated by either exchanging the HLH-LZ domains or reciprocally modifying LZ dimerization specificities. While transformation defective on their own, complementary mutants restore Myc transforming activity when coexpressed in cells. The HLH-LZ exchange mutants also have dominant negative activity on wild-type Myc function. In addition, wild-type max antagonizes myc function in a dose-dependent manner, presumably through competition of Max-Max and Myc-Max dimers for common target DNA sites. Therefore, Max can function as both suppressor and activator of Myc. A general model for the role of Myc and Max in growth control is discussed.

引用

页码：233 / 245

页数：13

共 66 条

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