PXD034333-1

PXD034333 is an original dataset announced via ProteomeXchange.

Title	Englerin A rewires phosphosignaling via HSP27 hyperphosphorylation to induce cytotoxicity in renal cancer cells
Description	Englerin A (EA) is a small molecule natural product with selective cytotoxicity against renal cancer cells. EA has been shown to induce apoptosis and cell death through cell cycle arrest and/or insulin signaling pathways. However, its specific biological mode of action or targets in renal cancer remains enigmatic. In this study, we employed advanced mass spectrometry-based phosphoproteomics approaches to identify EA’s functional roles in renal cancer. We identified 10,940 phosphorylation sites of which 706 sites exhibited EA-dependent phosphorylation changes. Integrated analysis of motifs and interaction networks suggested activation of stress-activated kinases including p38 upon EA treatment. Of note, a downstream target of p38, HSP27, was found to be hyperphosphorylated on multiple sites upon EA treatment. Among these, a novel site Ser65 on HSP27, which was further validated by targeted proteomics, was shown to be crucial for EA-induced cytotoxicity in renal cancer cells. Taken together, these data reveal the complex signaling cascade that is induced upon EA treatment and importantly provide insights onto its effects on downstream molecular signaling.
HostingRepository	PRIDE
AnnounceDate	2022-07-25
AnnouncementXML	Submission_2022-07-25_06:43:27.287.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Asfa Alli Shaik
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-06 01:10:31	ID requested
⏵ 1	2022-07-25 06:43:28	announced

Neo SP, Alli-Shaik A, Wee S, Lim Z, Gunaratne J, Englerin A Rewires Phosphosignaling via Hsp27 Hyperphosphorylation to Induce Cytotoxicity in Renal Cancer Cells. J Proteome Res, 21(8):1948-1960(2022) [pubmed]

submitter keyword: Englerin A, renal cancer, anti-cancer drug, phosphoproteomics, HSP27

Jayantha GUNARATNE
contact affiliation	Translational Biomedical Proteomics Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR, Singapore
contact email	jayanthag@imcb.a-star.edu.sg
lab head
Asfa Alli Shaik
contact affiliation	IMCB
contact email	asfaas@imcb.a-star.edu.sg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034333
     1. Label: PRIDE project
     2. Name: Englerin A rewires phosphosignaling via HSP27 hyperphosphorylation to induce cytotoxicity in renal cancer cells