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PXD021722

PXD021722 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHypoxia Regulates Overall mRNA Homeostasis by Inducing Met1-linked Linear Ubiquitination of AGO2 in Cancer Cells
DescriptionHypoxia is the most prominent feature in human solid tumors and induces activation of hypoxia-inducible factors and their downstream genes to promote cancer progression. However, whether and how hypoxia regulates overall mRNA homeostasis is unclear. Here we show that hypoxia inhibits global-mRNA decay in cancer cells. Mechanistically, hypoxia induces the interaction of AGO2 with HOIL-1L/HOIP, two crucial components of a linear ubiquitin chain assembly complex, which co-localizes with miRNA-induced silencing complex and in turn catalyzes AGO2 occurring Met1-linked linear ubiquitination (M1-Ubi). A series of biochemical experiments reveal that M1-Ubi of AGO2 restrains miRNA-mediated gene silencing. Moreover, combination analyses of the AGO2-associated mRNA transcriptome by RIP-Seq and the mRNA transcriptome by RNA-Seq confirm that AGO2 M1-Ubi interferes miRNA-targeted mRNA recruiting to AGO2, and thereby facilitates accumulation of global mRNAs. By this mechanism, short-term hypoxia may protect overall mRNAs and enhances stress tolerance, whereas long-term hypoxia in tumor cells results in seriously changing the entire gene expression profile to drive cell malignant evolution.
HostingRepositoryiProX
AnnounceDate2021-04-06
AnnouncementXMLSubmission_2023-03-01_23:11:24.296.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHailong Zhang
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListubiquitination signature dipeptidyl lysine
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-28 20:35:31ID requested
12023-03-01 23:11:26announced
Publication List
Keyword List
submitter keyword: Hypoxia, AGO2, miRISC, Met1-linked linear ubiquitination, Global mRNA homeostasis, mRNA decay
Contact List
Jianxiu Yu
contact affiliationShanghai Jiao Tong University school of medicine, Department of Biochemistry and Molecular Cell Biology
contact emailJianxiu.Yu@shsmu.edu.cn
lab head
Hailong Zhang
contact affiliationShanghai Jiao Tong University school of medicine, Department of Biochemistry and Molecular Cell Biology
contact emailzhanghailonghello@163.com
dataset submitter
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iProX dataset URI