PXD053956

PXD053956 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Itaconate Negatively Regulates Innate Signaling through Modification of IRAK4, Degradation of NFκB, and the Modulation of Global Ubiquitination
Description	A wide variety of electrophilic derivatives of the Kreb’s cycle-derived metabolite, itaconate, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages. Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production. Endogenous itaconate directly targets cysteine 13 in IRAK4 disrupting IRAK4 autophosphorylation and activation, drives the degradation of NFκB, and modulates global ubiquitination patterns. As a result, cells unable to make itaconate overproduce inflammatory cytokines such as TNFα, IL6, and IL-1β in response to these innate activators. In contrast, the production of IFNβ, downstream of LPS, requires the production of itaconate. These data demonstrate that itaconate is a critical arbiter of inflammatory cytokine production downstream of multiple innate signaling pathways laying the groundwork for the development of itaconate mimetics for the treatment of autoimmunity.
HostingRepository	jPOST
AnnounceDate	2024-07-16
AnnouncementXML	Submission_2024-07-15_10:54:35.733.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jesus A. Gutierrez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	unknown modification; unknown modification; unknown modification; L-methionine sulfoxide; alpha-amino acetylated residue
Instrument	instrument

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-15 10:35:08	ID requested
⏵ 1	2024-07-15 10:54:36	announced

Publication List

Dataset with its publication pending

Dataset with its publication pending

Keyword List

submitter keyword: Itaconate, THP1 cells, cysteine activity based protein profiling

submitter keyword: Itaconate, THP1 cells, cysteine activity based protein profiling

Contact List

Frank C. Dorsey
lab head
Jesus A. Gutierrez
contact affiliation	Eli Lilly and Company
dataset submitter

Full Dataset Link List

jPOST dataset URI
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jPOST dataset URI

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.jpostdb.org/JPST003216/