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  Characterization of the c-MYC-regulated transcriptome by SAGE: Identification and analysis of c-MYC target genes

Menssen, A., & Hermeking, H. (2002). Characterization of the c-MYC-regulated transcriptome by SAGE: Identification and analysis of c-MYC target genes. Proceedings of the National Academy of Sciences of the United States of America, 99(9), 6274-6279.

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Genre: Journal Article
Alternative Title : Proc. Natl. Acad. Sci. U. S. A.

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 Creators:
Menssen, A.1, Author              
Hermeking, H.2, Author              
Affiliations:
1Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565172              
2Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              

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 Abstract: To identify target genes of the oncogenic transcription factor c-MYC, serial analysis of gene expression (SAGE) was performed after adenoviral expression of c-MYC in primary human umbilical vein endothelial cells: 216 different SAGE tags, corresponding to unique mRNAs, were induced, whereas 260 tags were repressed after c-MYC expression (P < 0.05). The induction of 53 genes was confirmed by using microarray analysis and quantitative real-time PCR: among these genes was MetAP2/p67, which encodes an activator of translational initiation and represents a validated target for inhibition of neovascularization. Furthermore, c-MYC induced the cell cycle regulatory genes CDC2-L1, Cyclin E binding protein 1, and Cyclin B1. The DNA repair genes BRCA1, MSH2, and APEX were induced by c-MYC, suggesting that c-MYC couples DNA replication to processes preserving the integrity of the genome. MNT, a MAX-binding antagonist of c-MYC function, was upregulated, implying a negative feedback loop. In vivo promoter occupancy by c-MYC was detected by chromatin immunoprecipitation for CDK4, Prohibitin, MNT, Cyclin B1, and Cyclin E binding protein 1, showing that these genes are direct c-MYC targets. The c-MYC-regulated genes/tags identified here will help to define the set of bona fide c-MYC targets and may have potential therapeutic value for inhibition of cancer cell proliferation, tumor-vascularization, and restenosis.

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Language(s): eng - English
 Dates: 2002-04-30
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 38124
ISI: 000175377800095
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Title: Proceedings of the National Academy of Sciences of the United States of America
  Alternative Title : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 99 (9) Sequence Number: - Start / End Page: 6274 - 6279 Identifier: ISSN: 0027-8424