STRUCTURE-FUNCTION ANALYSIS OF THE MAF ONCOGENE PRODUCT, A MEMBER OF THE B-ZIP PROTEIN FAMILY

被引:138
作者
KATAOKA, K
NISHIZAWA, M
KAWAI, S
机构
[1] JAPANESE FDN CANC RES,INST CANC,DEPT VIRAL ONCOL,1-37-1 KAMI IKEBUKURO,TOSHIMA KU,TOKYO 170,JAPAN
[2] UNIV TOKYO,INST MED SCI,DEPT TUMOR VIRUS RES,MINATO KU,TOKYO 108,JAPAN
关键词
D O I
10.1128/JVI.67.4.2133-2141.1993
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The v-maf oncogene, identified as the transforming gene of the avian retrovirus AS42, encodes a protein containing a b-Zip motif. From this structural feature, the v-Maf protein was expected to form a dimer and function as a nuclear DNA-binding protein. In this study, we demonstrate that this protein indeed localizes predominantly in the nucleus and forms a homodimer through its leucine zipper structure. To delineate the structural requirement for the transforming activity, we constructed and characterized a panel of v-maf mutants harboring various deletions or point mutations. A region of about 100 amino acid residues located near its carboxyl terminus, which contains the b-Zip motif, was found to be essential for the basal transforming activity of v-Maf on chicken embryo fibroblasts. On the other hand, the amino-terminal two-thirds of the v-Maf protein seems to play a role in potentiating the transforming activity of v-Maf. It was also found that the c-maf proto-oncogene, without any structural modification in its protein-coding region, could transform cells as efficiently as could the v-maf oncogene when transduced by a retroviral vector. Thus, it is probably deregulated expression that makes the v-maf gene oncogenic. In addition, we discovered one point mutation, altering the structure of the b-Zip domain, which further enhances the transforming activity of the v-maf oncogene. Such mutant will be useful in exploring the mechanism of action of the Maf protein.
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页码:2133 / 2141
页数:9
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