Asset Details
Do you wish to reserve the book?
Translation from unconventional 5′ start sites drives tumour initiation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Translation from unconventional 5′ start sites drives tumour initiation
Do you wish to request the book?
Translation from unconventional 5′ start sites drives tumour initiation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Translation from unconventional 5′ start sites drives tumour initiation
2017
Overview
We are just beginning to understand how translational control affects tumour initiation and malignancy. Here we use an epidermis-specific,
in vivo
ribosome profiling strategy to investigate the translational landscape during the transition from normal homeostasis to malignancy. Using a mouse model of inducible SOX2, which is broadly expressed in oncogenic RAS-associated cancers, we show that despite widespread reductions in translation and protein synthesis, certain oncogenic mRNAs are spared. During tumour initiation, the translational apparatus is redirected towards unconventional upstream initiation sites, enhancing the translational efficiency of oncogenic mRNAs. An
in vivo
RNA interference screen of translational regulators revealed that depletion of conventional eIF2 complexes has adverse effects on normal but not oncogenic growth. Conversely, the alternative initiation factor eIF2A is essential for cancer progression, during which it mediates initiation at these upstream sites, differentially skewing translation and protein expression. Our findings unveil a role for the translation of 5′ untranslated regions in cancer, and expose new targets for therapeutic intervention.
The translation of upstream open reading frames in skin tumour models protects some cancer-related mRNAs from global reductions in protein synthesis during the early stages of tumour initiation, suggesting that unconventional translation has a crucial role in tumorigenesis.
Deregulated translation and tumour progression
Elaine Fuchs and colleagues uncover a role for the translation of upstream open reading frames (uORFs)—gene-expression regulatory elements present in many messenger RNAs—in skin tumour models. This oncogene-driven shift in translation shields some pro-tumorigenic mRNAs from global reductions in protein synthesis during the early stages of tumorigenesis, suggesting that tumour drivers may use uORF translation to enact oncogenic transformation.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
5' Untranslated Regions - genetics
/ Animals
/ Cancer
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - pathology
/ Eukaryotic Initiation Factor-2 - metabolism
/ Female
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Open Reading Frames - genetics
/ Peptide Chain Initiation, Translational - genetics
/ Peptides
/ Precancerous Conditions - genetics
/ Precancerous Conditions - metabolism
/ Precancerous Conditions - pathology
/ Proteins
/ Science
/ SOXB1 Transcription Factors - genetics
/ SOXB1 Transcription Factors - metabolism
/ Tumors
