Activation and repression of mammalian gene expression by the c-myc protein.

Genes and Development - Tập 1 Số 4 - Trang 347-357 - 1987
Rima Kaddurah‐Daouk1, J. M. Greene2, Albert S. Baldwin3, Robert E. Kingston2
1Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
2Harvard University
3Biology

Tóm tắt

One mechanism by which nuclear-localized oncogenes might transform cells is through an ability to regulate gene expression. We show that the c-myc protein stimulates the level of appropriately initiated expression from the human heat shock protein 70 (hsp70) promoter. Sequences required for full activation lie upstream of the transcription initiation site and are distinct from sequences necessary for basal expression. These sequences also appear distinct from promoter sequences necessary for heat induction, serum induction, and induction by the papovavirus T antigens. The c-myc protein inhibits appropriately initiated expression from the mouse metallothionein I (MT-I) promoter. A mutation that removes 138 amino acids of exon 2 produces a c-myc gene product that is capable of activating the hsp70 promoter but is no longer capable of inhibiting MT-I expression, suggesting that these two properties reside in different domains of the c-myc protein. Expression from the adenovirus EII promoter is slightly inhibited, while expression from the SV40 early promoter is minimally affected by the c-myc protein. Both the spectrum of promoters regulated by the c-myc protein and the sequence requirements for that regulation differ from those of previously characterized viral trans-activating proteins. The data suggest that the c-myc protein can both stimulate and inhibit transcription from mammalian promoters in a novel manner.

Từ khóa


Tài liệu tham khảo

10.1016/0092-8674(82)90159-3

10.1038/306274a0

10.1016/0092-8674(77)90272-0

10.1016/0092-8674(79)90333-7

10.1038/312608a0

10.1073/pnas.82.21.7299

10.1093/nar/9.15.3719

10.1038/296262a0

10.1073/pnas.77.11.6511

1982, Recombinant genomes which express chloramphenicol acetyl transferase in mammalian cells., Mol. Cell. Biol., 2, 1044

10.1016/0042-6822(73)90341-3

10.1016/0092-8674(83)90216-7

1982, Regulation in vivo of a mammalian gene: Cadmium induction of a mouse metallothionein gene in SV40 vectors., J. Mol. Appl. Genet., 1, 273

10.1016/0092-8674(83)90535-4

10.1073/pnas.82.19.6455

1984, Common control of the heat shock gene and early adenovirus genes: Evidence for a cellular EIa-like activity., Mol. Cell. Biol., 4, 867

10.1073/pnas.76.8.3665

1983, Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection., Mol. Cell. Biol., 3, 2058

1985, Analysis of an activatable promoter: Sequences in the simian virus 40 late promoter required for T antigen mediated transactivation., Mol. Cell. Biol., 5, 1859

1983, Simian virus 40 and polyomavirus induce synthesis of heat shock proteins in mammalian cells., Mol. Cell. Biol., 3, 1

10.1038/312280a0

1984, Regulation of transcription of the adenovirus EII promoter by Ela gene products: Absence of sequence specificity., Mol. Cell. Biol., 4, 1970

10.1016/0092-8674(85)90049-2

1986, Binding of polyomavirus large T antigen to the human hsp70 promoter is not required for trans-activation., Mol. Cell. Biol., 6, 3180

10.1126/science.2935935

10.1038/304596a0

10.1016/0092-8674(86)90704-X

1986, Stimulation of the adenovirus E2 promoter by simian virus 40 T antigen or EIa occurs by different mechanisms., Mol. Cell. Biol., 6, 2020

Maniatis, T., E. Fritsch, and J. Sambrook. 1982. Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.

1982, Regulation of heat shock genes: A DNA sequence upstream of Drosophila hsp70 genes is essential for their induction in monkey cells., EMBO J., 1, 1279, 10.1002/j.1460-2075.1982.tb00025.x

10.1016/0092-8674(82)90453-6

10.1016/0092-8674(82)90249-5

10.1016/0168-9525(85)90012-5

10.1016/0092-8674(86)90693-8

10.1126/science.6463648

10.1038/306803a0

10.1073/pnas.77.10.5706

10.1038/304602a0

10.1073/pnas.84.1.170

1986, Human growth hormone as a receptor gene in regulation studies using transient growth expression., Mol. Cell. Biol., 6, 3173

10.1016/0092-8674(82)90137-4

10.1073/pnas.83.16.5914

10.1126/science.325648

10.1016/0092-8674(85)90219-3

10.1073/pnas.82.18.6070

1985, Structure and expression of the human gene encoding major heat shock protein hsp70., Mol. Cell. Biol., 5, 330

10.1073/pnas.83.3.629

1986, The EIA 13S product of adenovirus 5 activates transcription of the cellular human hsp70 gene., Mol. Cell. Biol., 6, 2994

10.1073/pnas.83.15.5414