Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 350, Issue 4, Pages 834-841Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2006.09.128
Keywords
her-2; translation; ribosome; toeprinting; cancer; oncogene; uORF
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Funding
- NIAID NIH HHS [R01 AI026672, AI26672, R56 AI026672] Funding Source: Medline
- NIGMS NIH HHS [GM47498, R01 GM047498] Funding Source: Medline
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The her-2 (neu, erbB-2) oncogene encodes a 185-kDa transmembrane receptor tyrosine kinase. HER2 overexpression occurs in numerous primary human tumors and contributes to 25-30% of breast and ovarian carcinomas. Synthesis of HER2 is controlled in part by an upstream open reading frame (uORF) present in the transcript. We used synthetic capped and polyadenylated mRNAs containing sequences derived from the 5' region of the her-2 transcript fused to a firefly luciferase (LUC) reporter to examine this uORF's effect on translation in cell-free systems derived from reticulocytes, wheat germ and Neurospora crassa, and in RNA-transfected HeLa cells. The uORF reduced translation of the downstream cistron in all systems. [S-35]Met labeling of in vitro translation products obtained indicated that the uORF also affected downstream start-site selection. Primer extension inhibition (toeprint) assays of ribosomes loaded at initiation codons in reticulocyte lysates indicated that the uORF affected the interaction of ribosomes with the primary her-2 AUG codon. (c) 2006 Elsevier Inc. All rights reserved.
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