PXD029120-1

PXD029120 is an original dataset announced via ProteomeXchange.

Title	G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer
Description	SPOP, an E3 ubiquitin ligase, acts as a prostate-specific tumor suppressor with several key substrates mediating oncogenic function. However, the mechanisms underlying SPOP regulation are largely unknown. Here, we have identified G3BP1 as an interactor of SPOP and functions as a competitive inhibitor of Cul3SPOP, suggesting a distinctive mode of Cul3SPOP inactivation in prostate cancer (PCa). Transcriptomic analysis and functional studies reveal a G3BP1-SPOP ubiquitin signaling axis that promotes PCa progression through activating AR signaling. Moreover, AR directly upregulates G3BP1 transcription to further amplify G3BP1-SPOP signaling in a feed-forward manner. Our study supports a fundamental role of G3BP1 in disabling the tumor suppressive Cul3SPOP, thus defining a PCa cohort independent of SPOP mutation. Therefore, there are significantly more PCa that are defective for SPOP ubiquitin ligase than previously appreciated, and these G3BP1high PCa are more susceptible to AR-targeted therapy.
HostingRepository	PRIDE
AnnounceDate	2021-11-25
AnnouncementXML	Submission_2021-11-25_06:59:18.624.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chandrani Mukhopadhyay
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-13 23:04:06	ID requested
⏵ 1	2021-11-25 06:59:19	announced

Dataset with its publication pending

ProteomeXchange project tag: Human Proteome Project

submitter keyword: TAP-MS, Human, Prostate Cancer, SPOP, G3BP1

Pengbo Zhou
contact affiliation	Department of Pathology and Laboratory Medicine, The Joan and Stanford I. Weill Medical College of Cornell University, New York, NY 10065, USA
contact email	pez2001@med.cornell.edu
lab head
Chandrani Mukhopadhyay
contact affiliation	Weill Cornell Medicine
contact email	chm2067@med.cornell.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029120
     1. Label: PRIDE project
     2. Name: G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer