PXD030935

PXD030935 is an original dataset announced via ProteomeXchange.

Title	T cell activation decreases microRNA-15a/16 levels as a mechanism to promote MEK1-ERK1/2-Elk1 signaling for optimal proliferative capacity
Description	While microRNAs (miRs) have been extensively studied in the context of malignancy and tumor progression, their functions in regulating T cell activation are less clear. We found reduced levels of miR-15a/16 at 3-18 h post-T cell receptor (TCR) stimulation, suggesting a role in shaping T cell activation. An inducible miR15a/16 transgenic mouse model was developed to determine how elevating miR-15a/16 levels during early stages of activation would affect T cell proliferation and to identify TCR signaling pathways regulated by this miR pair. Doxycyclin (DOX) induced expression of miR-15a/16 from 0-18 h post-TCR stimulation decreased ex vivo proliferation as well as in vivo antigen-specific proliferation. Bioinformatic and proteomic approaches were combined to identify MEK1 as a target of miR-15a/16. MEK1 targeting by miR-15a/16 was confirmed using miR mimics that decreased MEK1 containing the 3’-UTR target nucleotide sequence (UGCUGCUA) but did not decrease MEK1 containing a mutated control sequence (AAAAAAAA). Phosphorylation of downstream signaling molecules ERK1/2 and Elk1 were decreased with DOX-induced miR-15a/16 expression. In addition to MEK1, ERK1 was subsequently found to be targeted by miR-15a/16, with DOX induced miR-15a/16 reducing total ERK1 levels in T cells. These findings show that TCR stimulation reduces miR-15a/16 levels at early stages of T cell activation to facilitate increased MEK1 and ERK1, and this promotes sustained MEK1-ERK1/2-Elk1 signaling required for optimal proliferation.
HostingRepository	PRIDE
AnnounceDate	2022-04-04
AnnouncementXML	Submission_2022-04-03_19:40:29.198.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD030935
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Stephanie Byrum
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-13 03:28:34	ID requested
⏵ 1	2022-04-03 19:40:29	announced

Urena F, Ma C, Hoffmann FW, Nunes LGA, Urschitz J, Moisyadi S, Khadka VS, Deng Y, Hoffmann PR, T-cell activation decreases miRNA-15a/16 levels to promote MEK1-ERK1/2-Elk1 signaling and proliferative capacity. J Biol Chem, 298(3):101634(2022) [pubmed]

submitter keyword: microRNA (miRNA), mitogen‐activated protein kinase (MAPK), cell cycle, cell growth, cell signaling

Peter Hoffmann
contact affiliation	Department of Cell and Molecular Biology, University of Hawaii at Manoa, Honolulu, Hawaii 96822
contact email	peterrh@hawaii.edu
lab head
Stephanie Byrum
contact affiliation	UAMS
contact email	sbyrum@uams.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030935
     1. Label: PRIDE project
     2. Name: T cell activation decreases microRNA-15a/16 levels as a mechanism to promote MEK1-ERK1/2-Elk1 signaling for optimal proliferative capacity