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Y705 and S727 are required for the mitochondrial import and transcriptional activities of STAT3, and for regulation of stem cell proliferation.
- Source :
-
Development (Cambridge, England) [Development] 2021 Sep 01; Vol. 148 (17). Date of Electronic Publication: 2021 Sep 06. - Publication Year :
- 2021
-
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 import of STAT3 inside mitochondria requires Y705 phosphorylation by Jak, whereas 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: although the Y705-mutated STAT3 cannot enter mitochondria, the S727 mutation does not affect import into the organelle and is responsible for STAT3-dependent mitochondrial transcription. Surprisingly, STAT3-dependent increase of mitochondrial transcription appears to be 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.<br />Competing Interests: Competing interests The authors declare no competing or financial interests.<br /> (© 2021. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Central Nervous System embryology
DNA, Mitochondrial metabolism
Embryo, Nonmammalian
Embryonic Stem Cells metabolism
Extracellular Signal-Regulated MAP Kinases metabolism
Intestines embryology
Janus Kinases metabolism
Mutation
Phosphorylation
STAT3 Transcription Factor genetics
Signal Transduction
Transcription, Genetic
Transcriptional Activation
Zebrafish
Zebrafish Proteins genetics
Cell Proliferation
Embryonic Stem Cells cytology
Mitochondria metabolism
STAT3 Transcription Factor metabolism
Zebrafish Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 148
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 34473253
- Full Text :
- https://doi.org/10.1242/dev.199477