PXD037104

PXD037104 is an original dataset announced via ProteomeXchange.

Title	Hypoxia stabilizes SETDB1 to maintain genome stability
Description	Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins (PHD) and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element (TE)-derived double-stranded RNAs (dsRNAs), thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:08:08.100.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ga Seul Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; acetylated residue; monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-30 04:02:21	ID requested
⏵ 1	2024-01-26 06:08:08	announced

10.1093/nar/gkad796;

Park S, Cho JH, Kim JH, Park M, Park S, Kim SY, Kim SK, Kim K, Park SG, Park BC, Moon JH, Lee G, Kim S, Kim JA, Kim JH, Hypoxia stabilizes SETDB1 to maintain genome stability. Nucleic Acids Res, 51(20):11178-11196(2023) [pubmed]

submitter keyword: Transposable Element,SETDB1, Genome instability, VHL, proline hydroxylation, Inflammation, Innate immune response, Hypoxia

Jeong-Hoon Kim
contact affiliation	1Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea
contact email	jungaekim@kribb.re.kr
lab head
Ga Seul Lee
contact affiliation	Korea Research Institute of Bioscience & Biotechnology (KRIBB)
contact email	rktmf1013@kribb.re.kr
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/2024/01/PXD037104

PRIDE project URI

• PRIDE
  1. PXD037104
     1. Label: PRIDE project
     2. Name: Hypoxia stabilizes SETDB1 to maintain genome stability