PXD044473

PXD044473 is an original dataset announced via ProteomeXchange.

Title	Succinylation of SERCA2a at lysine 352 promotes its ubiquitinoylation and degradation by proteasome in septic cardiomyopathy
Description	Intracellular Ca2+ cycle is rigorously modulated to govern effective myocardial systolic contraction and diastolic relaxation. Sarco/endoplasmic reticulum Ca2+ ATPase type 2a (SERCA2a) plays a crucial role in controlling intracellular Ca2+ signals and myocardial cell function. SERCA2a has been shown to be down-regulated and inactivated during myocardial dysfunction induced by sepsis. However, the causes of SERCA2a dysregulation in septic cardiomyopathy have not been fully elucidated yet. In this study, we delved into the effect of lysine succinylation on SERCA2a in lipopolysaccharide (LPS) -induced septic cardiomyopathy. A global succinylome of myocardial tissues from septic rats was performed. We identified 10324 succinylated lysine sites including 1,042 differentially succinylated lysine sites in the heart tissues in response to LPS. We developed a protein language model-based framework to prioritize the succinylation at K352 of SERCA2a which was functionally important and further analysis revealed a crosstalk between ubiquitination and succinylation of SERCA2a. SERCA2a was hypersuccinylated in the myocardial tissues of septic rats and LPS-treated cardiomyocytes. Increased ubiquitination level and reduced protein level and activity of SERCA2a were observed along with the increased succinylation of SERCA2a in vivo and in vitro. K352 was essential for the succinylation modulation of SERCA2a. Succinylation at K352 reduced the SERCA2a protein level, through fostering the formation of K48 ubiquitin chain on SERCA2a and its degradation by proteasome. Co-IP combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify SIRT2, a deacylase, as an interacting protein of SERCA2a. Further studies showed that SIRT2 decreased the succinylation at K352 of SERCA2a, suggesting that SIRT2 may function as a desuccinylase for SERCA2a. Collectively, our study identified a mechanism whereby SERCA2a is controlled by a crosstalk of post-translational modifications between succinylation and ubiquitinoylation.
HostingRepository	iProX
AnnounceDate	2023-08-10
AnnouncementXML	Submission_2023-08-09_20:38:42.099.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tiening Zhang
SpeciesList	scientific name: Rattus rattus; NCBI TaxID: 10117;
ModificationList	N6-succinyl-L-lysine
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-09 20:38:33	ID requested
⏵ 1	2023-08-09 20:38:42	announced

Dataset with its publication pending

submitter keyword: Post-translational modifications, septic cardiomyopathy, SERCA2a

SIRT2, succinylation, ubiquitinoylation

Tiening Zhang
contact affiliation	Shengjing Hospital of China Medical University
contact email	cmuztn@vip.qq.com
lab head
Tiening Zhang
contact affiliation	Shengjing Hospital of China Medical University
contact email	cmuztn@vip.qq.com
dataset submitter

iProX dataset URI