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Y705 and S727 are required for mitochondrial import and transcriptional activities of STAT3 and regulate proliferation of embryonic and tissue stem cells by Margherita Peron; Giacomo Meneghetti; Alberto Dinarello; Laura Martorano; Riccardo M. Betto; Nicola Facchinello; Annachiara Tesoriere; Natascia Tiso; Graziano Martello; Francesco Argenton is a scholarly article available to read on EtoBox.

What is Y705 and S727 are required for mitochondrial import and transcriptional activities of STAT3 and regulate proliferation of embryonic and tissue stem cells about?

## 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 determinedin vivothat 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 Jak2, 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: Y705 mutated STAT3 cannot enter the mitochondrion while the S727 mutation does not affect mitochondrial import of the protein. 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 JAK/STAT3 pathway or genetic ablation ofstat3gene, demonstrated that STAT3 is also required for cell proliferation in the intestine of zebrafish.

Author

Margherita Peron; Giacomo Meneghetti; Alberto Dinarello; Laura Martorano; Riccardo M. Betto; Nicola Facchinello; Annachiara Tesoriere; Natascia Tiso; Graziano Martello; Francesco Argenton

Publisher

Cold Spring Harbor Laboratory

Published

2020

Language

EN