PXD017731

PXD017731 is an original dataset announced via ProteomeXchange.

Title	Identification of Cytosolic Protein Targets of Catechol Estrogens in Breast Cancer Cells Using a Click Chemistry-based Workflow
Description	Catechol estrogens (CEs) are known to be toxic metabolites and the initiators in the oncogenesis of breast cancers via forming covalent adducts with DNAs. CEs shall also react with proteins but their cellular protein targets remain un-explored. Here we reported the identification of protein targets of CEs in the soluble cytosol of estrogen-sensitive breast cancer cells by multiple comparative proteomics using liquid chromatography tandem mass spectrometry (LC-MS/MS) coupled with an improved click chemistry-based workflow. Multiple comparative proteomics composed of experimental pair (probe versus solvent) and two control pairs (solvent versus solvent and probe versus solvent without enrichment), were studied using stable isotope dimethyl labeling. The use of 4-hydroxyethynylestradiol (4OHEE2) probe with an amide-free linker coupled with on-bead digestion and re-digestion of the proteins cleaved from the beads was shown to greatly improve the recovery and identification of CEs-adducted peptides. A total of 310 protein targets and 35 adduction sites were repeatedly (n≥2) identified with D/H (probe/solvent) ratio >4 versus only one identified with D/H >4 from the two control pairs, suggesting that our workflow imposes only a very low background. Meanwhile, multiple comparative D/H ratios revealed that CEs may down-regulate many target proteins involved in the metabolism or detoxification, suggesting a negative correlation between CEs-induced adduction and expression of proteins acting on the alleviation of stress-induced cellular damages. The reported method and data shall provide opportunities to study the progression of estrogen metabolism-derived diseases and biomarkers.
HostingRepository	PRIDE
AnnounceDate	2020-09-28
AnnouncementXML	Submission_2020-09-27_23:33:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Quynh-Trang Do
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; dimethylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-26 02:44:06	ID requested
⏵ 1	2020-09-27 23:33:10	announced

Do QT, Huang TE, Liu YC, Tai JH, Chen SH, Identification of Cytosolic Protein Targets of Catechol Estrogens in Breast Cancer Cells Using a Click Chemistry-Based Workflow. J Proteome Res, 20(1):624-633(2021) [pubmed]

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Catechol estrogens, breast cancer cells, affinity purification, proteomic, mass spectrometry

Shu-Hui Chen
contact affiliation	Department of Chemistry, National Cheng Kung University, Taiwan
contact email	shchen@ncku.edu.tw
lab head
Quynh-Trang Do
contact affiliation	National Cheng Kung University
contact email	nana251195@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017731
     1. Label: PRIDE project
     2. Name: Identification of Cytosolic Protein Targets of Catechol Estrogens in Breast Cancer Cells Using a Click Chemistry-based Workflow