PXD037262

PXD037262 is an original dataset announced via ProteomeXchange.

Title	Targeting phosphorylation of 17β-hydroxysteroid dehydrogenase 13 at serine 33 to treat nonalcoholic steatohepatitis
Description	17β-hydroxysteroid dehydrogenase-13 (17β-HSD13) is a liver-rich lipid droplet associated protein, encoding by gene HSD17B13, that acted as an important regulator of hepatic lipid metabolism. Increased expression of 17β-HSD13 promotes hepatic lipid accumulation in rodents, and a common loss-of-function variant of HSD17B13 (rs72613567: TA) is related to better outcome in patients with various chronic liver diseases. To understand the role of 17β-HSD13 in liver lipid metabolism under normal and high-fat feeding conditions, we characterized the effect of protein phosphorylation of 17β-HSD13 on hepatic lipid homeostasis. We identify Ser33 as an important protein kinase A (PKA)-mediated phosphorylation site of 17β-HSD13 that physically interact with ATGL and facilitates its translocation to lipid droplets to enhance lipolysis. Mutation of Ser33 to Ala (S33A) in 17β-HSD13 reduces ATGL-dependent lipolysis and increases lipid droplet size in cultured hepatocytes by reducing CGI-58-mediated ATGL activation. Consistently, a transgenic knock-in mouse strain carrying HSD17B13 S33A mutation (HSD17B1333A/A) spontaneously develops liver steatosis with reduced lipolysis. Moreover, HSD17B1333A/A mice are more prone to high fat-induced hepatic steatosis and inflammation. Finally, we found Reproterol, a potential HSD17B13 modulator and FDA-approved drug, confers a protection against liver steatosis possibly through phosphorylation of 17β-HSD13 at Ser33 in a PKA-dependent manner. In summary, we demonstrate a critical role and the underlying mechanism of hepatic 17β-HSD13 phosphorylation in the pathogenesis of NAFLD. Our findings highlight the potential of targeting 17β-HSD13 phosphorylation as a novel therapeutic approach for NAFLD.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:37:36.601.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD037262
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Rongfeng Lan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-10 07:53:47	ID requested
1	2023-03-10 23:06:21	announced
⏵ 2	2023-11-14 08:37:37	announced	2023-11-14: Updated project metadata.

Su W, Wu S, Yang Y, Guo Y, Zhang H, Su J, Chen L, Mao Z, Lan R, Cao R, Wang C, Xu H, Zhang C, Li S, Gao M, Chen X, Zheng Z, Wang B, Liu Y, Liu Z, Wang Z, Liu B, Fan X, Zhang X, Guan Y, -hydroxysteroid dehydrogenase 13 at serine 33 attenuates nonalcoholic fatty liver disease in mice. Nat Commun, 13(1):6577(2022) [pubmed]

10.6019/PXD037262;

submitter keyword: Human, LC-MSMS, 17β-HSD13 protein Gel band, 293T cell

Wen Su
contact affiliation	Shenzhen University
contact email	casufa@163.com
lab head
Rongfeng Lan
contact affiliation	Shenzhen University
contact email	lan@szu.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/2023/03/PXD037262

PRIDE project URI

• PRIDE
  1. PXD037262
     1. Label: PRIDE project
     2. Name: Targeting phosphorylation of 17β-hydroxysteroid dehydrogenase 13 at serine 33 to treat nonalcoholic steatohepatitis