ArticleOncogene2016
Comprehensive translational control of tyrosine kinase expression by upstream open reading frames.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Upstream open reading frames: new players in the landscape of cancer gene regulation.NAR cancer · 2024Review
- Ribo-uORF: a comprehensive data resource of upstream open reading frames (uORFs) based on ribosome profiling.Nucleic acids research · 2023Article
- Protein synthesis control in cancer: selectivity and therapeutic targeting.The EMBO journal · 2022Review
- Upstream open reading frames regulate translation of cancer-associated transcripts and encode HLA-presented immunogenic tumor antigens.Cellular and molecular life sciences : CMLS · 2022Article
- A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor.Biomedicines · 2021Article
- Somatic Functional Deletions of Upstream Open Reading Frame-Associated Initiation and Termination Codons in Human Cancer.Biomedicines · 2021Article
- Impact of uORFs in mediating regulation of translation in stress conditions.BMC molecular and cell biology · 2021Article
- Translational reprogramming marks adaptation to asparagine restriction in cancer.Nature cell biology · 2019Article
- The Untranslated Regions of mRNAs in Cancer.Trends in cancer · 2019Review
- Genome-wide maps of ribosomal occupancy provide insights into adaptive evolution and regulatory roles of uORFs during Drosophila development.PLoS biology · 2018Article
- A comprehensive catalog of predicted functional upstream open reading frames in humans.Nucleic acids research · 2018Article
- Loss-of-function uORF mutations in human malignancies.Scientific reports · 2018Article
- Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy.Targeted oncology · 2017Article
- Translational effects and coding potential of an upstream open reading frame associated with DOPA Responsive Dystonia.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- In vivo evidence that eIF3 stays bound to ribosomes elongating and terminating on short upstream ORFs to promote reinitiation.Nucleic acids research · 2017Article
- Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress.Nature cell biology · 2017Article
- Auxin Signaling in Regulation of Plant Translation Reinitiation.Frontiers in plant science · 2017Review
- Decoding sORF translation - from small proteins to gene regulation.RNA biology · 2016Review
- Article
- Upstream ORFs are prevalent translational repressors in vertebrates.The EMBO journal · 2016Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-transcriptional control has emerged as a major regulatory event in gene expression and often occurs at the level of translation initiation. Although overexpression or constitutive activation of tyrosine kinases (TKs) through gene amplification, translocation or mutation are well-characterized oncogenic events, current knowledge about translational mechanisms of TK activation is scarce. Here, we report the presence of translational cis-regulatory upstream open reading frames (uORFs) in the majority of transcript leader sequences of human TK mRNAs. Genetic ablation of uORF initiation codons in TK transcripts resulted in enhanced translation of the associated downstream main protein-coding sequences (CDSs) in all cases studied. Similarly, experimental removal of uORF start codons in additional non-TK proto-oncogenes, and naturally occurring loss-of-uORF alleles of the c-met proto-oncogene (MET) and the kinase insert domain receptor (KDR), was associated with increased CDS translation. Based on genome-wide sequence analyses we identified polymorphisms in 15.9% of all human genes affecting uORF initiation codons, associated Kozak consensus sequences or uORF-related termination codons. Together, these data suggest a comprehensive role of uORF-mediated translational control and delineate how aberrant induction of proto-oncogenes through loss-of-function mutations at uORF initiation codons may be involved in the etiology of cancer. We provide a detailed map of uORFs across the human genome to stimulate future research on the pathogenic role of uORFs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.