PXD013196-1

PXD013196 is an original dataset announced via ProteomeXchange.

Title	PTENa/b paradoxically promote carcinogenesis through WDR5-H3K4me3 axis
Description	PTEN, a widely investigated tumor suppressor, has at least two longer translational variants, PTEN and . However, the regulation and precise roles of endogenous PTEN/ in tumorigenesis remain greatly unknown. Here we show that USP9X and FBXW11 selectively regulate the stability of PTEN/ but not PTEN proteins by deubiqitination and ubiquitination respectively. USP9X promotes and FBXW11 suppresses tumorigenesis mediated by PTEN/. In contrast to the current paradigm for PTEN as a tumor suppressor, PTEN/ promote tumorigenesis of cancer cells in a phosphatase-independent manner. Mechanistically, PTEN/ localized in the nucleus regulate expressions of tumor-promoting genes such as NOTCH3 in the similar way as the H3K4 presenter WDR5. Further, PTEN/ but not PTEN directly interact with WDR5 to promote trimethylation of H3K4 and maintain a tumor-promoting signature. Taken together, our results indicate that PTEN/ are a double-edged sword for carcinogenesis, suggesting that reinterpretation of the importance of PTEN gene in carcinogenesis is warranted.
HostingRepository	PRIDE
AnnounceDate	2019-11-14
AnnouncementXML	Submission_2019-11-14_02:00:39.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD013196
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	ge mengkai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Deamidated; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-22 09:35:54	ID requested
⏵ 1	2019-11-14 02:14:29	announced

Shen SM, Zhang C, Ge MK, Dong SS, Xia L, He P, Zhang N, Ji Y, Yang S, Yu Y, Zheng JK, Yu JX, Xia Q, Chen GQ, promote carcinogenesis through WDR5 and H3K4 trimethylation. Nat Cell Biol, 21(11):1436-1448(2019) [pubmed]

submitter keyword: PTENa

PTENb

PTEN

USP9X

FBXW11

ubiquitination;WDR5

Carcinogenesis

Guo-Qiang Chen
contact affiliation	Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
contact email	chengq@shsmu.edu.cn
lab head
ge mengkai
contact affiliation	SJTU
contact email	gemengk@sjtu.edu.cn
dataset submitter

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/2019/11/PXD013196

PRIDE project URI

• PRIDE
  1. PXD013196
     1. Label: PRIDE project
     2. Name: PTENa/b paradoxically promote carcinogenesis through WDR5-H3K4me3 axis