PXD029645

PXD029645 is an original dataset announced via ProteomeXchange.

Title	The tumor suppressor Fhit in complex with the alarmone Ap3A binds to the ribosome and impedes translation
Description	Upon cellular stress, the concentration of the alarmone diadenosine triphosphate (Ap3A) increases and is thought to trigger downstream adaptive processes. The known Ap3A-hydrolase fragile histidine triad (Fhit) is known to form a complex with Ap3A. The molecular mechanism of Fhit-Ap3A signaling is however unknown. In this study, by synthesizing a covalent Fhit-Ap3A complex we have elucidated the Ap3A-dependent cellular interactome by mass spectrometry-based proteome profiling. Interestingly, we found a significant enrichment of proteins involved in translation. We then show that Fhit translocates from the nucleolus into the cytosol upon stress to form a Fhit-Ap3A complex which impedes translation both in vitro and in vivo in an Ap3A dependent manner resulting in reduced cell viability. Overall, our findings provide a mechanistic model by which the tumor suppressor Fhit collaborates with the alarmone Ap3A to regulate cellular proliferation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:32:54.468.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-10 07:33:50	ID requested
1	2022-12-20 06:07:25	announced
⏵ 2	2023-11-14 08:32:55	announced	2023-11-14: Updated project metadata.

Herzog D, Jansen J, Mi, ß, un M, Diederichs K, Stengel F, Marx A, A Elucidates Its Inhibitory Action on Translation. J Am Chem Soc, 144(19):8613-8623(2022) [pubmed]

submitter keyword: AP-MS, mass spectrometry, ribosome, XL-MS,Fhit, Ap3A, translation

Andreas Marx
contact affiliation	Department of Chemistry University of Konstanz
contact email	andreas.marx@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029645
     1. Label: PRIDE project
     2. Name: The tumor suppressor Fhit in complex with the alarmone Ap3A binds to the ribosome and impedes translation