PXD042626-1

PXD042626 is an original dataset announced via ProteomeXchange.

Title	p38γ and p38δ modulate innate immune response by regulating MEF2D activation
Description	Evidence implicating p38γ and p38δ (p38γ/p38δ) in inflammation are mainly based on experiments using p38γ/p38δ deficient (p38γ/δ-/-) mice, which show low levels of TPL2, the kinase upstream of MKK1-ERK1/2 in myeloid cells. This could obscure p38γ/p38δ roles, since TPL2 is essential for regulating inflammation. Here we generated a p38γD171A/D171A/p38δ-/- (p38γ/δKIKO) mouse, expressing kinase-inactive p38γ and lacking p38δ. This mouse exhibited normal TPL2 levels, making it an excellent tool to elucidate specific p38γ/p38δ functions. p38γ/δKIKO mice showed a reduced inflammatory response and less susceptibility to LPS-induced septic shock and Candida albicans infection than wild-type mice. Gene expression analyses in LPS-activated WT and p38γ/δKIKO macrophages revealed that p38γ/p38δ regulated numerous genes implicated in innate immune response. Additionally, phospho-proteomic analyses and in vitro kinase assays showed that the transcription factor myocyte enhancer factor-2D (MEF2D) was phosphorylated at Ser444 via p38γ/p38δ. Mutation of MEF2D Ser444 to the non-phosphorylatable residue Ala increased its transcriptional activity and the expression of iNOS and IL-1β mRNA. These results suggest that p38γ/p38δ govern innate immune responses by regulating MEF2D phosphorylation and transcriptional activity.
HostingRepository	PRIDE
AnnounceDate	2023-08-10
AnnouncementXML	Submission_2023-08-10_05:40:04.079.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042626
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	EricBonneil
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-01 10:17:48	ID requested
⏵ 1	2023-08-10 05:40:04	announced
2	2023-11-14 09:04:37	announced	2023-11-14: Updated project metadata.

10.6019/PXD042626;

Esc, ó, s A, Diaz-Mora E, Pattison M, Fajardo P, Gonz, á, lez-Romero D, Risco A, Mart, í, n-G, ó, mez J, Bonneil É, Sonenberg N, Jafarnejad SM, Sanz-Ezquerro JJ, Ley SC, Cuenda A, modulate innate immune response by regulating MEF2D activation. Elife, 12():(2023) [pubmed]

submitter keyword: inflammation, MEF2D, p38δ, phosphorylation,p38γ

AnaCuenda
contact affiliation	Centro Nacional de Biotecnología, Madrid, Spain
contact email	acuenda@cnb.csic.es
lab head
EricBonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042626
     1. Label: PRIDE project
     2. Name: p38γ and p38δ modulate innate immune response by regulating MEF2D activation