PXD021722

PXD021722 is an original dataset announced via ProteomeXchange.

Title	Hypoxia Regulates Overall mRNA Homeostasis by Inducing Met1-linked Linear Ubiquitination of AGO2 in Cancer Cells
Description	Hypoxia 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.
HostingRepository	iProX
AnnounceDate	2021-04-06
AnnouncementXML	Submission_2023-03-01_23:11:24.296.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hailong Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-28 20:35:31	ID requested
⏵ 1	2023-03-01 23:11:26	announced

Zhang H, Zhao X, Guo Y, Chen R, He J, Li L, Qiang Z, Yang Q, Liu X, Huang C, Lu R, Fang J, Cao Y, Huang J, Wang Y, Huang J, Chen GQ, Cheng J, Yu J, -linked linear ubiquitination of AGO2 in cancer cells. Nat Commun, 12(1):5416(2021) [pubmed]

submitter keyword: Hypoxia, AGO2, miRISC, Met1-linked linear ubiquitination, Global mRNA homeostasis, mRNA decay

Jianxiu Yu
contact affiliation	Shanghai Jiao Tong University school of medicine, Department of Biochemistry and Molecular Cell Biology
contact email	Jianxiu.Yu@shsmu.edu.cn
lab head
Hailong Zhang
contact affiliation	Shanghai Jiao Tong University school of medicine, Department of Biochemistry and Molecular Cell Biology
contact email	zhanghailonghello@163.com
dataset submitter

iProX dataset URI