PXD028933

PXD028933 is an original dataset announced via ProteomeXchange.

Title	Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma
Description	The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which drive tumor growth and treatment resistance.To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown reduced SOX2 transcriptional activity, self-renewal capacity, and in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance.
HostingRepository	PRIDE
AnnounceDate	2021-11-04
AnnouncementXML	Submission_2021-11-04_02:44:44.607.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028933
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Albert Kim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-04 10:02:38	ID requested
⏵ 1	2021-11-04 02:44:44	announced

Dataset with its publication pending

submitter keyword: E3 ligase, TRIM26, WWP2, SOX2, glioblastoma, brain cancer

Albert H. Kim
contact affiliation	Department of Neurological Surgery, Washington University in St. Louis School of Medicine
contact email	alberthkim@wustl.edu
lab head
Albert Kim
contact affiliation	Washington University in St. Louis
contact email	alberthkim@wustl.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028933
     1. Label: PRIDE project
     2. Name: Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma