PXD035401

PXD035401 is an original dataset announced via ProteomeXchange.

Title	A Quantitative Assessment of Arsenite-induced Perturnation of Ubiquitinated Proteome
Description	Arsenic contamination in food and ground water constitutes a public health concern to more than 100 million people worldwide. Individuals chronically exposed to arsenic through drinking and ingestion exhibit a higher risk in developing cancers and cardiovascular diseases. Nevertheless, the underlying mechanisms of arsenic toxicity are not fully understood. Arsenite is known to bind to and deactivate RING finger E3 ubiquitin ligases; thus, we reason that a systematic interrogation about how arsenite exposure modulates global protein ubiquitination may reveal novel molecular targets for arsenic toxicity. By employing liquid chromatography-tandem mass spectrometry, in combination with stable isotope labeling by amino acids in cell culture (SILAC) and immunoprecipitation of di-glycine-conjugated lysine-containing tryptic peptides, we assessed the alterations in protein ubiquitination in GM00637 human skin fibroblast cells upon arsenite exposure at the entire proteome level. We observed that arsenite exposure led to altered ubiquitination of many proteins, where the alterations in a large majority of ubiquitination events are negatively correlated with changes in expression of the corresponding proteins, suggesting their modulation by the ubiquitin-proteasomal pathway. Moreover, we observed that arsenite exposure confers diminished ubiquitination of a rate-limiting enzyme in cholesterol biosynthesis, HMGCR, at Lys248. In addition, we revealed that TRC8 is the major E3 ubiquitin ligase for HMGCR ubiquitination in HEK293T cells, and the arsenite-induced diminution of HMGCR ubiquitination is abrogated with depletion of TRC8. In summary, we systematically characterized arsenite-induced perturbations in ubiquitinated proteome in human cells, and found that the arsenite-elicited diminution of HMGCR ubiquitination involves TRC8.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:55.971.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JI JIANG
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 00:23:41	ID requested
1	2023-10-24 11:00:43	announced
⏵ 2	2023-11-14 09:07:02	announced	2023-11-14: Updated project metadata.

Jiang J, Wang Y, Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol, 35(9):1589-1597(2022) [pubmed]

ProteomeXchange project tag: Human Proteome Project

submitter keyword: arsneite exposure, ubiquitome,human cells, data dependent acuisition, immunocapture, SILAC lableing, LC-MS/MS

Yinsheng Wang; Ji Jiang
contact affiliation	Department of Chemistry, University of California, Riverside, California 92521-0403, United States
contact email	yinsheng@ucr.edu
lab head
JI JIANG
contact affiliation	UCR
contact email	jijiang0315@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035401
     1. Label: PRIDE project
     2. Name: A Quantitative Assessment of Arsenite-induced Perturnation of Ubiquitinated Proteome