PUBLICATION
Phosphorylation of ELAVL1 (Ser219/Ser316) mediated by PKC is required for erythropoiesis
- Authors
- Zhou, X., Wang, S., Zheng, M., Kuver, A., Wan, X., Dai, K., Li, X.
- ID
- ZDB-PUB-181106-30
- Date
- 2018
- Source
- Biochimica et biophysica acta. Molecular cell research 1866(2): 214-224 (Journal)
- Registered Authors
- Li, Xi, Wan, Xiaoyang
- Keywords
- Erythropoiesis, Nucleocytoplasmic transport, PKC, Zebrafish development, elavl1
- MeSH Terms
-
- Animals
- Cell Differentiation
- Cell Line, Tumor
- ELAV-Like Protein 1/metabolism*
- ELAV-Like Protein 1/physiology
- Erythropoiesis/genetics*
- Erythropoiesis/physiology*
- GATA1 Transcription Factor/genetics
- GATA1 Transcription Factor/metabolism
- Gene Expression Regulation, Developmental/genetics
- Hemin/pharmacology
- Humans
- K562 Cells
- Phosphorylation
- Protein Kinase C/metabolism
- Protein Kinase C/physiology
- RNA, Messenger/metabolism
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 30395882 Full text @ BBA Molecular Cell Research
Citation
Zhou, X., Wang, S., Zheng, M., Kuver, A., Wan, X., Dai, K., Li, X. (2018) Phosphorylation of ELAVL1 (Ser219/Ser316) mediated by PKC is required for erythropoiesis. Biochimica et biophysica acta. Molecular cell research. 1866(2):214-224.
Abstract
Elavl1 (also known as HuR), an RNA binding protein highly conserved between zebrafish and human, regulates gene expression by stabilizing target mRNA. Our previous studies have uncovered that the predominant isoform elavl1a is required for zebrafish embryonic erythropoiesis. However, the exact mechanism of how elav11 spatiotemporally stabilizes target mRNAs to regulate specific erythropoiesis is not yet understood. Here we show that phosphorylation of elavl1a at Ser219 and Ser316 by PKC is necessarily required for cytosolic shuttling from the nucleus to stabilize gata1 mRNA and thus promotes erythropoiesis. Knockdown of elavl1a resulted in the hindrance of erythropoiesis and Hemin-induced erythroid differentiation of human myeloid leukemia K562 cells. Interestingly, inhibition of PKC reproduced the phenotype seen during zebrafish embryogenesis and erythroid differentiation of myeloid leukemia. Mechanistically, Hemin induced elavl1a export from nuclear to cytoplasmic space in K562 cells in a manner dependent on phosphorylation on Ser219 and Ser316, as overexpression of elavl1a with mutations on Ser219 and Ser316 resulted in erythropoiesis failure. Additionally, co-administration of low doses of elavl1a morpholino (MO) and three PKC inhibitors showed a combined effect in zebrafish embryonic erythropoiesis dysplasia. In conclusion, our study reveals that PKC-mediated phosphorylation of elavl1a at Ser219 and Ser316 sites controls its nucleo-cytoplasmic translocation in zebrafish, thereby regulating embryonic erythropoiesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping