PUBLICATION
Y705 and S727 are required for mitochondrial import and transcriptional activities of STAT3 and regulate proliferation of embryonic and tissue stem cells
- Authors
- Peron, M., Dinarello, A., Meneghetti, G., Martorano, L., Betto, R.M., Facchinello, N., Tesoriere, A., Tiso, N., Martello, G., Argenton, F.
- ID
- ZDB-PUB-210903-7
- Date
- 2021
- Source
- Development (Cambridge, England) 148(17): (Journal)
- Registered Authors
- Argenton, Francesco, Facchinello, Nicola, Tiso, Natascia
- Keywords
- ESC, STAT3, mitochondria, transcription, zebrafish
- MeSH Terms
-
- Animals
- Cell Proliferation*
- Central Nervous System/embryology
- DNA, Mitochondrial/metabolism
- Embryo, Nonmammalian
- Embryonic Stem Cells/cytology*
- Embryonic Stem Cells/metabolism
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Intestines/embryology
- Janus Kinases/metabolism
- Mitochondria/metabolism*
- Mutation
- Phosphorylation
- STAT3 Transcription Factor/genetics
- STAT3 Transcription Factor/metabolism*
- Signal Transduction
- Transcription, Genetic
- Transcriptional Activation
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34473253 Full text @ Development
Citation
Peron, M., Dinarello, A., Meneghetti, G., Martorano, L., Betto, R.M., Facchinello, N., Tesoriere, A., Tiso, N., Martello, G., Argenton, F. (2021) Y705 and S727 are required for mitochondrial import and transcriptional activities of STAT3 and regulate proliferation of embryonic and tissue stem cells. Development (Cambridge, England). 148(17):.
Abstract
The STAT3 transcription factor, acting both in the nucleus and mitochondria, maintains embryonic stem cell pluripotency and promotes their proliferation. In this work, using zebrafish, we determined in vivo that mitochondrial STAT3 regulates mtDNA transcription in embryonic and larval stem cell niches and that this activity affects their proliferation rates. As a result, we demonstrated that STAT3 import inside mitochondria requires Y705 phosphorylation by Jak, while its mitochondrial transcriptional activity, as well as its effect on proliferation, depends on the MAPK target S727. These data were confirmed using mouse embryonic stem cells: while the Y705 mutated STAT3 cannot enter mitochondria, the S727 mutation does not affect the import in the organelle and is responsible for STAT3-dependent mitochondrial transcription. Surprisingly, STAT3-dependent increase of mitochondrial transcription seems independent from STAT3 binding to STAT3 responsive elements. Finally, loss of function experiments, with chemical inhibition of the JAK/STAT3 pathway or genetic ablation of stat3 gene, demonstrated that STAT3 is also required for cell proliferation in the intestine of zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping