STRUCTURAL AND FUNCTIONAL-ANALYSIS OF THE HUMAN METALLOTHIONEIN-IA GENE - DIFFERENTIAL INDUCTION BY METAL-IONS AND GLUCOCORTICOIDS

被引:298
作者
RICHARDS, RI
HEGUY, A
KARIN, M
机构
[1] AUSTRALIAN NATL UNIV, RES SCH BIOL SCI, CTR RECOMBINANT DNA RES, CANBERRA, ACT 2601, AUSTRALIA
[2] AUSTRALIAN NATL UNIV, RES SCH BIOL SCI, DEPT GENET, CANBERRA, ACT 2601, AUSTRALIA
[3] UNIV SO CALIF, DEPT MICROBIOL, LOS ANGELES, CA 90033 USA
关键词
D O I
10.1016/0092-8674(84)90322-2
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
A region of human DNA containing 4 metallothionein (hMT) genes is described. One of these genes, hMT-IA, encodes a functional protein that confers heavy metal resistance to NIH 3T3 cells after transfer on a bovine papilloma virus-derived vector. This gene is expressed in cultured human cell lines, but at a lower basal level than the hMT-IIA gene; it shows a different induction response to heavy metals and glucocorticoids than the hMT-IIA gene. Induction of the human MT family therefore does not represent an equivalent elevation in the level of expression of individual genes, but is the sum of the differential responses of active members. The differential response is due to functional differences of the respective promoter/regulatory regions of the genes as shown by gene-infusion experiments. While the hMT-IIA promoter is responsive to Cd2+, Zn2+ and glucocorticoids, the hMT-IA promoter mediates response only to Cd2+.
引用
收藏
页码:263 / 272
页数:10
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