Abstract:
:Based on transfection into cells in culture or natural transduction into retroviruses, proto-ras genes seem to derive transforming function either from heterologous promoters or from point mutations. Here we ask how such different events could achieve the same results. To identify homologous regulatory elements, about 3 kilobases of rat DNA upstream of the first untranslated proto-Ha-ras exon was sequenced. Surprisingly, the sequence shares at -1858 a homology of 148 nucleotides with Harvey (Ha) sarcoma virus, 5' of viral ras, signaling possibly a second untranslated proto-Ha-ras exon. In addition the sequence contains a perfect repeat of 25 CA dinucleotides at -2655. A retroviral promoter, even from upstream of the poly(CA), conferred transforming function on proto-Ha-ras and increased transcription greater than 100-fold compared with that of unrearranged proto-ras. Point mutations were not necessary for transforming function of rat and human proto-Ha-ras genes with retroviral promoters but did enhance it greater than 10-fold. A unifying hypothesis proposes that proto-ras genes depend on high expression from heterologous promoters or enhancers for transforming function, which is modulated by ras point mutations. The hypothesis makes two testable predictions. (i) Unrearranged proto-ras genes with point mutations, which occur in some cancers, have no transforming function. Indeed, tumors with mutated proto-ras genes, even those that also lack hypothetical tumor-suppressor genes, are indistinguishable from counterparts with normal proto-ras genes. (ii) Proto-ras genes in transfected cells derive transforming function from heterologous promoters or enhancers acquired via illegitimate recombination from vector DNAs and particularly from viral helper genes that must be cotransfected for transformation of primary cells. Indeed, expression of exogenous proto-ras genes in cells transformed by transfection is as high as for viral ras genes and is much higher than in the cells of origin.
journal_name
Proc Natl Acad Sci U S Aauthors
Chakraborty AK,Cichutek K,Duesberg PHdoi
10.1073/pnas.88.6.2217subject
Has Abstractpub_date
1991-03-15 00:00:00pages
2217-21issue
6eissn
0027-8424issn
1091-6490journal_volume
88pub_type
杂志文章abstract::Natural killer (NK) cells recognize alloantigens on normal cells. One of these alloantigens correlates with homozygosity for a dimorphism of HLA-C at positions 77-80, which is shared by a number of HLA-C alleles. A second allelic alloantigen correlates with homozygosity for the alternative HLA-C dimorphism, which is s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.90.24.12000
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.93.19.10446
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2015-06-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1988-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1995-01-03 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1994-03-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1978-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2007-02-27 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
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更新日期:2010-05-11 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2010-03-23 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1988-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1980-08-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-01-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2009-03-17 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2016-11-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2011-03-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.6.2072
更新日期:1990-03-01 00:00:00
abstract::Synthesis of mouse metallothionein (MT)-I and MT-II is transcriptionally induced by the synthetic glucocorticoid, dexamethasone (DEX) or both in vivo as well as in numerous cell lines. However, the location(s) of a glucocorticoid response element (GRE) has not been described. The observation that a marked MT-I gene, a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.19.10045
更新日期:1997-09-16 00:00:00