PXD035635

PXD035635 is an original dataset announced via ProteomeXchange.

Title	Epigenetic Control over IFN Type-I Response antagonizes self-renewal in acute myeloid leukemia
Description	Large biological heterogeneity hallmarks acute myeloid leukemia (AML) and substantially hampers development of novel comprehensive therapies. While all-trans retinoic acid (ATRA) revolutionized therapy of acute promyelocytic leukemia, its impact on other AML subtypes remained largely disappointing. Here we show for the first time that ATRA mediated phosphorylation of the histone demethylase PHF8 induces apoptosis of AML cells of different subtypes via regulation of viral mimicry and subsequent initiation of interferon (IFN) type-I response. Phospho-PHF8 conferred H3K9me2 demethylation at promoter sites of key initiators of cell-intrinsic immune response. Multiomics based analyses revealed activation of cytosolic RNA sensors as key step towards NF-κB driven IFN type-I mediated apoptosis. Epigenetic changes directed by PHF8 also induced a specific proteosome pathway controlling NF-κB activity after its initial activation. Hence, PHF8 orchestrates viral mimicry, triggering IFN type-I response-differentiation-apoptotic network in a broad spectrum of AML when activated by ATRA. Forced phosphorylation of PHF8 via combination treatment with ATRA and simultaneous pharmacological inhibition of PHF8 dephosphorylation significantly impaired growth of human AML. Our findings finally open the gate for successful application of ATRA-based combination therapies in AML.
HostingRepository	PRIDE
AnnounceDate	2024-06-22
AnnouncementXML	Submission_2024-06-22_11:22:32.193.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ashokkumar Jayavelu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-29 09:01:26	ID requested
⏵ 1	2024-06-22 11:22:33	announced

Felipe Fumero E, Walter C, Frenz JM, Seifert F, Alla V, Hennig T, Angenendt L, Hartmann W, Wolf S, Serve H, Oellerich T, Lenz G, M, ü, ller-Tidow C, Schliemann C, Huber O, Dugas M, Mann M, Jayavelu AK, Mikesch JH, Arteaga MF, Epigenetic control over the cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia. Blood, 143(22):2284-2299(2024) [pubmed]

10.1182/blood.2023021640;

submitter keyword: AML, PHF8, ATRA, Proteome, Phosphoproteome

Dr.Ashok Kumar Jayavelu
contact affiliation	Proteomics and Cancer Cell Signaling Unit, German Cancer Research center(DKFZ), Heidelberg, Germany
contact email	ak.jayavelu@dkfz-heidelberg.de
lab head
Ashokkumar Jayavelu
contact affiliation	Dept Proteomics and Signal Transduction, MaxPlanck Institute of Biochemistry
contact email	jayavelu@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD035635

PRIDE project URI

• PRIDE
  1. PXD035635
     1. Label: PRIDE project
     2. Name: Epigenetic Control over IFN Type-I Response antagonizes self-renewal in acute myeloid leukemia