PXD020327

PXD020327 is an original dataset announced via ProteomeXchange.

Title	Activation of FAM111A Protease Induces Defects in Nuclear Function that Likely Underlie its Roles in Disease and Viral Restriction
Description	Mutations in the nuclear trypsin-like serine protease FAM111A cause Kenny-Caffey syndrome (KCS2) with hypoparathyroidism and skeletal dysplasia, or perinatally lethal osteocraniostenosis (OCS). In addition, FAM111A was identified as a restriction factor for certain host range mutants of the SV40 polyomavirus and VACV orthopoxvirus. However, because FAM111A function is poorly characterized, its roles in restricting viral replication and the etiology of KCS2 and OCS remain undefined. We find that the FAM111A KCS2 and OCS patient mutants are hyperactive, inducing apoptosis-like phenotypes in a protease-dependent manner. Similarly, in response to the attempted replication of SV40 host range mutants in restrictive cells, FAM111A activity induces the loss of nuclear barrier function and structure. Interestingly, pan-caspase inhibitors do not block FAM111A-dependent phenotypes such as nuclear “leakiness”, shrinkage and pore redistribution, implying it acts independently or upstream of caspases. In this regard, we identified nucleoporins and the associated GANP transcription factor as FAM111A interactors and candidate targets. Together our data provide key insight into how FAM111A activation can restrict viral replication, and how its deregulated activity could cause KCS2 and OCS
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:15:43.311.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020327
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yasi Jami
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-13 00:56:49	ID requested
1	2020-11-24 22:23:34	announced
2	2021-01-04 05:56:40	announced	2021-01-04: Updated publication reference for PubMed record(s): 33369867.
⏵ 3	2024-10-22 05:15:47	announced	2024-10-22: Updated project metadata.

10.6019/PXD020327;

10.15252/embr.202050803;

Nie M, Oravcov, á M, Jami-Alahmadi Y, Wohlschlegel JA, Lazzerini-Denchi E, Boddy MN, FAM111A induces nuclear dysfunction in disease and viral restriction. EMBO Rep, 22(2):e50803(2021) [pubmed]

submitter keyword: FAM111A,SV40polyomavirus,KCS2,VACV,Mass spectrometry,OCS

Michael N. Boddy
contact affiliation	Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
contact email	nboddy@scripps.edu
lab head
Yasi Jami
contact affiliation	University of California Los Angeles
contact email	yjami@ucla.edu
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/2020/11/PXD020327

PRIDE project URI

• PRIDE
  1. PXD020327
     1. Label: PRIDE project
     2. Name: Activation of FAM111A Protease Induces Defects in Nuclear Function that Likely Underlie its Roles in Disease and Viral Restriction