PXD002648 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | De-novo synthesized targets of NMD and ER stress |
Description | Nonsense-mediated mRNA decay (NMD) has originally been described as a surveillance mechanism to inhibit the expression of mRNAs with truncated open reading frames (ORFs) and to contribute to the fidelity of gene expression. It is now recognized that NMD also controls the expression of physiological genes with “intact” mRNA. Stress can decrease NMD efficiency and thus increase the mRNA levels of physiological NMD targets. As stress can also inhibit translation, the net outcome for shaping the proteome is difficult to predict. We have thus analyzed de-novo protein synthesis in response to NMD inhibition or the induction of mild endoplasmic reticulum (ER) stress by treatment of cells with the reducing agent dithiotreitol (DTT). We combined pulsed azidohomoalanine (AHA) and stable isotope labeling by amino acids in cell culture (SILAC). Labeled proteins were purified by click chemistry-based covalent coupling to agarose beads, trypsinized, fractionated, and analyzed by LC-MS/MS. We find that mild ER stress upregulates the de-novo synthesis of components of all three branches of the unfolded protein response (PERK, IRE1a and ATF6) without increasing eIF2a phosphorylation or impairing of protein translation. In contrast, inhibition of NMD induces de-novo protein synthesis of downstream targets of the PERK and IRE1a pathways but not the ATF6 pathway. These data thus support a model that implicates a positive feedback loop of ER stress inhibiting NMD efficiency which further promotes the ER stress response in a branch-specific manner. |
HostingRepository | PRIDE |
AnnounceDate | 2016-02-22 |
AnnouncementXML | Submission_2016-02-22_00:31:00.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jana Sieber |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-08-03 00:49:48 | ID requested | |
⏵ 1 | 2016-02-22 00:31:01 | announced | |
Publication List
Sieber J, Hauer C, Bhuvanagiri M, Leicht S, Krijgsveld J, Neu-Yilik G, Hentze MW, Kulozik AE, Proteomic Analysis Reveals Branch-specific Regulation of the Unfolded Protein Response by Nonsense-mediated mRNA Decay. Mol Cell Proteomics, 15(5):1584-97(2016) [pubmed] |
Keyword List
curator keyword: Technical |
submitter keyword: AHA, click chemistry, pulsed SILAC, NMD, UPF1, UPR, DTT |
Contact List
Andreas E. Kulozik |
contact affiliation | Department of Pediatric Oncology, Hematology, Immunology and Pulmonology University Medical Center for Children and Adolescents Im Neuenheimer Feld 430 D-69120 Heidelberg Germany ( lab head ) |
contact email | andreas.kulozik@med.uni-heidelberg.de |
lab head | |
Jana Sieber |
contact affiliation | Heidelberg University |
contact email | j_loeber@gmx.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/02/PXD002648 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002648
- Label: PRIDE project
- Name: De-novo synthesized targets of NMD and ER stress