Information de reference pour ce titreAccession Number: | 00004686-199604010-00017.
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Author: | Lee, Linda A. *; Dolde, Christine ***; Barrett, John *; Wu, Chyi S. *; Dang, Chi V. **********
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Institution: | *Departments of Medicine, **Molecular Biology & Genetics, ***Program in Human Genetics & Molecular Biology, and ****The Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Address correspondence to Dr. Chi V. Dang, Ross Research Building, Room 1025, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205. Phone: 410-955-2773; FAX: 410-955-0185. Received for publication 11 September 1995 and accepted in revised form 19 January 1996.
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Title: | A Link between c-Myc-mediated Transcriptional Repression and Neoplastic Transformation.[Article]
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Source: | Journal of Clinical Investigation. 97(7):1687-1695, April 1, 1996.
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Abstract: | Recent studies indicate that the transcription factor c-Myc contributes to oncogenesis by altering the expression of genes involved in cell proliferation, but its precise function in neoplasia remains ambiguous. The ability of c-Myc to bind the sequence CAC(G/A)TG and transactivate appears to be linked to its transforming activity; however, c-Myc also represses transcription in vitro through a pyrimidinerich cis element termed the initiator (Inr). In transfection experiments using the adenoviral major late (adML) promoter, which contains two Myc binding sites and an Inr, we determined that c-Myc represses transcription through the initiator in vivo. This activity requires the dimerization domain and amino acids 106 to 143, which are located within the transactivation domain and are necessary for neoplastic transformation. We studied a lymphoma-derived c-Myc substitution mutation at 115-Phe, which is within the region required for transcriptional suppression, and found the mutant more effective than wild-type c-Myc in transforming rodent fibroblasts and in suppressing the adML promoter. Our studies of both loss-of-function and gain-of-function c-Myc mutations suggest a link between c-Myc-mediated neoplastic transformation and transcriptional repression through the Inr. (J. Clin. Invest. 1996. 97:1687-1695.) Key words: transrepression centered dot bHLH centered dot basic-helix-loop-helix centered dot Burkitt lymphoma
Copyright (C) 1996 The American Society for Clinical Investigation, Inc.
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Language: | English.
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Document Type: | Articles.
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Journal Subset: | Clinical Medicine. Life Sciences.
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ISSN: | 0021-9738
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NLM Journal Code: | hs7, 7802877
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