PXD044782

PXD044782 is an original dataset announced via ProteomeXchange.

Title	DNA damage stress control is a tLT- and EHMT2-dependent central feature of Merkel Cell Carcinoma
Description	Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high mortality rate. Merkel cell polyomavirus (MCPyV) is the etiology of 80% of MCC cases via expression of the viral oncogenes small T antigen (sT) and truncated large T antigen (tLT). These proteins impair the Rb1-dependent G1/S checkpoint blockade and subvert the host cell epigenome to promote proliferation and evade immune detection. Through whole proteome analysis and proximal interactomics, we identified a tLT-dependent deregulation of DNA damage response (DDR) proteins. We investigated a novel protein proximal interaction between tLT and the histone methyltransferase EHMT2. In this regard, TA knockdown in MCC cells reduced DDR protein levels and increased levels of the DNA damage marker γH2Ax. EHMT2 normally promotes H3K9 methylation and DDR signaling. Given that inhibition of EHMT2 did not result in extensive proteomic changes, we hypothesized that the tLT-EHMT2 interaction could be involved in DDR pathway deregulation. In the presence of tLT, we report that EHMT2 gained double and single-strand break repair proximal interactors. EHMT2 inhibition rescued proliferation in MCC cells depleted for their T antigens, suggesting impaired DDR and/or lack of cell cycle checkpoint efficiency. Combined tLT and EHMT2 inhibition led to altered DDR signaling, evidenced by multiple alterations in signal transduction. Together, our data strongly suggest that tLT hijacks multiple components of the DNA damage machinery to enhance tolerance to DNA damage in MCC cells which could be at the basis of, the remarkable genetic stability of these cancers.
HostingRepository	PRIDE
AnnounceDate	2024-06-04
AnnouncementXML	Submission_2024-06-04_05:59:05.698.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kamel Bachiri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 02:25:27	ID requested
⏵ 1	2024-06-04 05:59:06	announced

Dataset with its publication pending

submitter keyword: Merkel Cell Carcinoma

truncated LT

EHMT2

proximal interactomics

proteome analysis

DNA Damage Repair signaling.

Michel Salzet
contact affiliation	Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000, Lille, France
contact email	michel.salzet@univ-lille.fr
lab head
Kamel Bachiri
contact affiliation	Laboratoire PRISM - INSERM U1192 - Bât. SN3 Université de Lille, Sciences et Technologies - 59655 Villeneuve d´Ascq
contact email	kamel.bch@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044782
     1. Label: PRIDE project
     2. Name: DNA damage stress control is a tLT- and EHMT2-dependent central feature of Merkel Cell Carcinoma