PXD035283

PXD035283 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin E3 ligase FBXO21 regulates cytokine mediated signaling pathways, but is dispensable for steady-state hematopoiesis
Description	Hematopoietic cell fate decisions such as self-renewal and differentiation are highly regulated through multiple molecular pathways. One pathway, the ubiquitin proteasome system (UPS), controls protein levels by tagging them with polyubiquitin chains and promoting their degradation through the proteasome. Ubiquitin E3 ligases serve as the substrate-recognition component of the UPS. Through investigating the FBOX family of E3 ligases, we discovered that Fbxo21 was highly expressed in the hematopoietic stem and progenitor cell (HSPC) population, and showed low to no expression in mature myeloid populations. To determine the role of FBXO21 on HSPC maintenance, self-renewal, and differentiation, we generated shRNAs against FBXO21 and a hematopoietic specific Fbxo21 conditional knockout (cKO) mouse model. We found that silencing FBXO21 in HSPCs led to a loss in colony formation and an increase in cell differentiation in vitro. Additionally, stressing the HSPC populations in our Fbxo21 cKO mouse with 5-FU injections resulted in a decrease in survival, despite these populations showing minimal alterations during steady-state hematopoiesis. Although FBXO21 has previously been proposed to regulate cytokine signaling via ASK and p38, our results show that depletion of FBXO21 led to altered ERK signaling in vitro. Together, these findings suggest ubiquitin E3 ligase FBXO21 regulates HSPCs through cytokine mediated pathways.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:29:34.499.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Samantha Swenson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; ubiquitination signature dipeptidyl lysine; phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-13 04:25:04	ID requested
1	2022-11-11 15:05:45	announced
⏵ 2	2023-11-14 07:29:35	announced	2023-11-14: Updated project metadata.

Wittorf KJ, Weber KK, Swenson SA, Buckley SM, Ubiquitin E3 ligase FBXO21 regulates cytokine-mediated signaling pathways, but is dispensable for steady-state hematopoiesis. Exp Hematol, 114():33-42.e3(2022) [pubmed]

submitter keyword: FBOX,Hematopoietic Stem Cell, Ubiquitin E3 Ligase

Shannon Mychel Buckley
contact affiliation	University of Nebraska Medical Center School of Medicine Department of Genetics, Cell Biology, & Anatomy Buckley Lab Omaha, Nebraska United States of America
contact email	shannon.buckley@unmc.edu
lab head
Samantha Swenson
contact affiliation	University of Nebraska Medical Center
contact email	samantha.swenson@unmc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035283
     1. Label: PRIDE project
     2. Name: Ubiquitin E3 ligase FBXO21 regulates cytokine mediated signaling pathways, but is dispensable for steady-state hematopoiesis