PUBLICATION

Irf2bp2a regulates liver development via stabilizing P53 protein in zebrafish

Authors
Yan, L., Gao, S., Zhu, J., Zhou, J.
ID
ZDB-PUB-220611-17
Date
2022
Source
Biochimica et biophysica acta. General subjects   1866(10): 130186 (Journal)
Registered Authors
Zhu, Jun
Keywords
C/ebpα, Liver, Zebrafish, irf2bp2a, p53
MeSH Terms
  • Animals
  • Humans
  • Liver/metabolism
  • Proto-Oncogene Proteins c-mdm2/genetics
  • Proto-Oncogene Proteins c-mdm2/metabolism
  • Tumor Suppressor Protein p53*/genetics
  • Tumor Suppressor Protein p53*/metabolism
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics
PubMed
35688336 Full text @ BBA General Subjects
Abstract
Zebrafish irf2bp2a, an ortholog of human IRF2BP2, is specifically expressed in the developing liver at growth stage. As a multi-functional protein, the role of irf2bp2a during hepatogenesis remains unclear. Here we take advantage of an irf2bp2a knockout line to show that the deficiency of irf2bp2a can induce apoptosis of hepatic cells through aberrant p53 activation at the early stage of embryonic development. Mechanistic studies reveal that within the IRF2BP2-null hepatic cells, more MDM2 molecules, the E3 ubiquitin ligase of P53, can be sequestrated into the IRF2-MDM2 complex, which in turns stabilizes P53 protein. Moreover, irf2bp2a is demonstrated as a direct downstream target of c/ebpα. Thus, a C/ebpα-Irf2bp2a-P53 axis controls liver development in zebrafish. Overall, our findings indicate a stage-specific role of irf2bp2a on liver organogenesis by regulating p53 pathway.
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping