PXD040891

PXD040891 is an original dataset announced via ProteomeXchange.

Title	MDM2 influences ACE2 stability and SARS-Cov2 uptake
Description	The Angiotensin-converting enzyme 2 (ACE2) receptor is the central entry point for SARS-Cov2. Several SAR-Cov2 substrains have developed mutations in their spike protein to maximize their use of ACE2, e.g. to strengthen ACE2 binding for increased uptake or adapt to specific amino acid properties of ACE2 to cross the species barrier. But little is known about the effect of host regulators on ACE2 and subsequently their impact on SARS-Cov2 infection. Here we identify the E3 ligase MDM2 as a ACE2 modulator. The knockout of MDM2 induced a strong pro-viral effect specific for SARS-Cov2 and we could see the increase of ACE2 levels. This effect is likely dependent on the ubiquitination site Lysine 788, which MDM2 uses to induce proteasomal degradation of ACE2. Substituting this amino acid led to increased ACE2 levels and increased SARS-CoV2 infection facilitated by enhanced SARS-Cov2 uptake.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:05:10.319.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Quirin Emslander
SpeciesList	scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: NCBITaxon:2697049; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-15 07:17:28	ID requested
1	2023-09-08 04:34:00	announced
⏵ 2	2023-11-14 09:05:13	announced	2023-11-14: Updated project metadata.

Emslander Q, Krey K, Hamad S, Maidl S, Oubraham L, Hesse J, Henrici A, Austen K, Mergner J, Grass V, Pichlmair A, MDM2 Influences ACE2 Stability and SARS-CoV-2 Uptake. Viruses, 15(8):(2023) [pubmed]

submitter keyword: Human, Ubiquitination, SARS-CoV2, ACE2

Andreas Pichlmair
contact affiliation	Technical University Munich, Faculty of Medicine, Institute of Virology - Viral Immunopathology, Schneckenburger Str. 8, D-81675 Munich, Germany
contact email	Andreas.Pichlmair@tum.de
lab head
Quirin Emslander
contact affiliation	TUM
contact email	quirin.emslander@tum.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/2023/09/PXD040891

PRIDE project URI

• PRIDE
  1. PXD040891
     1. Label: PRIDE project
     2. Name: MDM2 influences ACE2 stability and SARS-Cov2 uptake