PUBLICATION

Irf2bp2a regulates terminal granulopoiesis through proteasomal degradation of Gfi1aa in zebrafish

Authors
Gao, S., Wang, Z., Wang, L., Wang, H., Yuan, H., Liu, X., Chen, S., Chen, Z., de Thé, H., Zhang, W., Zhang, Y., Zhu, J., Zhou, J.
ID
ZDB-PUB-210806-5
Date
2021
Source
PLoS Genetics   17: e1009693 (Journal)
Registered Authors
Chen, Zhu, Zhang, Wenqing, Zhang, Yiyue, Zhu, Jun
Keywords
none
MeSH Terms
  • Humans
  • Gene Knockout Techniques
  • Leukopoiesis
  • HEK293 Cells
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • DNA-Binding Proteins/genetics*
  • DNA-Binding Proteins/metabolism
  • Animals
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Gene Expression Regulation
  • Male
  • Feedback, Physiological
  • Proteolysis
  • Female
  • Proteasome Endopeptidase Complex/metabolism*
  • HL-60 Cells
(all 19)
PubMed
34351909 Full text @ PLoS Genet.
Abstract
The ubiquitin-proteasome system plays important roles in various biological processes as it degrades the majority of cellular proteins. Adequate proteasomal degradation of crucial transcription regulators ensures the proper development of neutrophils. The ubiquitin E3 ligase of Growth factor independent 1 (GFI1), a key transcription repressor governing terminal granulopoiesis, remains obscure. Here we report that the deficiency of the ring finger protein Interferon regulatory factor 2 binding protein 2a (Irf2bp2a) leads to an impairment of neutrophils differentiation in zebrafish. Mechanistically, Irf2bp2a functions as a ubiquitin E3 ligase targeting Gfi1aa for proteasomal degradation. Moreover, irf2bp2a gene is repressed by Gfi1aa, thus forming a negative feedback loop between Irf2bp2a and Gfi1aa during neutrophils maturation. Different levels of GFI1 may turn it into a tumor suppressor or an oncogene in malignant myelopoiesis. Therefore, discovery of certain drug targets GFI1 for proteasomal degradation by IRF2BP2 might be an effective anti-cancer strategy.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
rj30TgTransgenic Insertion
    szy5
      Small Deletion
      zf3610
        Small Deletion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        gfi1aaMO1-gfi1aaMRPHLNO
        irf2bp2aMO1-irf2bp2aMRPHLNO
        1 - 2 of 2
        Show
        Fish
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
        Show
        Mapping
        No data available