PXD032956-1

PXD032956 is an original dataset announced via ProteomeXchange.

Title	SUMOylation controls the rapid transcriptional reprogramming induced by chemotherapies in Acute Myeloid Leukemias
Description	Genotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some of their non-DNA-damaging effects are also instrumental for killing dividing cells. We report here that the anthracycline Daunorubicin (DNR), one of the main drugs used to treat Acute Myeloid Leukemia (AML), induces broad transcriptional changes in AML cells before cell death induction. The regulated genes are particularly enriched in genes controlling cell proliferation and death, as well as inflammation and immunity. These transcriptional changes are preceded by DNR-dependent deSUMOylation of chromatin proteins, which limits both the positive and negative effects of DNR on transcription. Quantitative proteomics shows that proteins that are deSUMOylated in response to DNR are mostly transcription factors, transcriptional co-regulators and chromatin organizers. Among them, the CCCTC-binding factor CTCF is highly enriched at SUMO-binding sites found in cis-regulatory regions. This is notably the case at the promoter of the DNR-induced NFKB2 gene. Its induction is preceded by a SUMO-dependent reconfiguration of chromatin loops engaging its CTCF- and SUMO-bound promoter with distal cis-regulatory regions. Altogether, our work suggests that one of the earliest effects of DNR in AML cells is a SUMO-dependent transcriptional reprogramming.
HostingRepository	PRIDE
AnnounceDate	2023-06-23
AnnouncementXML	Submission_2023-06-23_09:56:39.913.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AnaMartinez-Val
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	sumoylated lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-02 15:04:52	ID requested
⏵ 1	2023-06-23 09:56:40	announced
2	2024-10-22 05:50:26	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: SUMO, Acute Myeloid Leukemias

Jesper VelgaardOlsen
contact affiliation	Group leader, Professor University of Copenhagen Faculty of Health and Medical Sciences Novo Nordisk Foundation Center for Protein Research Denmark
contact email	jesper.olsen@cpr.ku.dk
lab head
AnaMartinez-Val
contact affiliation	Novo Nordisk Foundation Center for Protein Research
contact email	ana.mdval@cpr.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032956
     1. Label: PRIDE project
     2. Name: SUMOylation controls the rapid transcriptional reprogramming induced by chemotherapies in Acute Myeloid Leukemias