PXD015830

PXD015830 is an original dataset announced via ProteomeXchange.

Title	PPARgamma ubiquitination sites in HEK293T cells
Description	Peroxisome proliferator–activated receptor γ (PPARγ) is the central regulator of adipogenesis, and its dysregulation is linked to obesity and metabolic diseases. Identification of the factors that regulate PPARγ expression and activity is therefore crucial for combating obesity. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with a known role in xenobiotic detoxification. Recent studies have suggested that AhR also plays essential roles in energy metabolism. However, the detailed mechanisms remain unclear. We previously reported that experiments with adipocyte-specific Cullin 4b (Cul4b)-knockout mice showed that CUL4B suppresses adipogenesis by targeting PPARγ. Here, using immunoprecipitation, ubiquitination, real-time PCR and Gst-pulldown assays, we report that AhR functions as the substrate receptor in CUL4B–RING E3 ubiquitin ligase (CRL4B) complex and is required for recruiting PPARγ. AhR overexpression reduced PPARγ stability and suppressed adipocyte differentiation, and AhR knockdown stimulated adipocyte differentiation in 3T3-L1 cells. Furthermore, we found that two lysine sites on residues 268 and 293 in PPARγ are targeted for CRL4B-mediated ubiquitination, indicating cross-talk between acetylation and ubiquitination. Our findings establish a critical role of AhR in regulating PPARγ stability and suggest that the AhR–PPARγ interaction may represent a potential therapeutic target for managing metabolic diseases arising from PPARγ dysfunction.
HostingRepository	PRIDE
AnnounceDate	2019-11-01
AnnouncementXML	Submission_2019-11-01_05:00:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hao Dou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-15 06:00:31	ID requested
⏵ 1	2019-11-01 05:00:12	announced

Dataset with its publication pending

submitter keyword: PPARgamma LC-MS/MS HEK293T

Yaoqin Gong
contact affiliation	Institute of Molecular Medicine and Genetics,Shandong University, PR China
contact email	yxg8@sdu.edu.cn
lab head
Hao Dou
contact affiliation	Associate Professor
contact email	douhao@sdu.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/PXD015830

PRIDE project URI

• PRIDE
  1. PXD015830
     1. Label: PRIDE project
     2. Name: PPARgamma ubiquitination sites in HEK293T cells