PXD006059-2

PXD006059 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	The Interplay between K63-linked Polyubiquitinated DDX17 and m6A-modified miRNAs Regulates Hypoxia-induced Tumor Initiation
Description	DEAD-box RNA-binding proteins (RBPs) play a significant role in RNA metabolism to achieve cellular homeostasis, including miRNA biogenesis and transcription. Hypoxia induces stemness cell-like characteristics in cancer cells and promotes malignant progression. Despite the fact that hypoxia can induce the changes in protein and RNA modification, thereby regulating downstream gene expressions, how modifications at different molecular layers interplay with each other are poorly understood. Here we show that hypoxia induces HectH9-mediated K63-linked polyubiquitination of the DEAD-box protein DDX17 as well as reduces N6-methyladenosine (m6A) marks in pri-miRNAs. While m6A potentiates DDX17 binding to pri-miRNAs, decreased m6A modifications of pri-miRNAs and increased polyubiquitination of DDX17 under hypoxia lead to decreased DDX17 binding to pri-miRNAs binding. These events enhance the association of DDX17 with the ubiquitin receptor p300 and lead to a decrease in miRNA biogenesis, especially for miRNAs regulating stemness and stemness-related genes. In addition, polyubiquitinated DDX17 together with p300 upregulates H3K56Ac levels on the stemness and stemness-related genes, resulting in enhancement of tumor initiating ability. Post-transcriptionally, decreased miRNA production, including those targeting stemness genes or stemness-related genes, also facilitates tumor initiation. Together, hypoxia triggers DDX17 poly-ubiquitination, which orchestrates dual mechanisms to increase tumor initiating ability and promote tumor progression.
HostingRepository	jPOST
AnnounceDate	2018-03-09
AnnouncementXML	Submission_2018-09-19_00:06:34.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yi-Ting Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide
Instrument	Orbitrap Fusion; TripleTOF 5600

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-08 19:21:28	ID requested
1	2018-03-08 07:00:05	announced
⏵ 2	2018-09-19 00:06:34	announced	Updated CV, FTP location and Modification list.
3	2021-02-04 17:05:36	announced	2021-02-04: Updated FTP location.
4	2022-09-18 03:43:16	announced	2022-09-18: Updated FTP location.

Publication List

Dataset with its publication pending

Dataset with its publication pending

Keyword List

submitter keyword: PPI, cancer tumor, Label-free

submitter keyword: PPI, cancer tumor, Label-free

Contact List

Kou-Juey Wu
lab head
Yi-Ting Wang
contact affiliation	Center for genomic medicine, kyoto university
dataset submitter

Full Dataset Link List

jPOST dataset URI
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://jpost.pharm.kyoto-u.ac.jp/repository/JPST000240

jPOST dataset URI

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://jpost.pharm.kyoto-u.ac.jp/repository/JPST000240