Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival DOI Creative Commons
Wen Wei,

Xueqin Gao,

Jiawei Qian

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 135(3)

Published: Nov. 26, 2024

Proper control of inflammatory responses is essential for embryonic development, but the underlying mechanism poorly understood. Here, we show that under physiological conditions, inactivation ISG15, an inflammation amplifier, associated with interaction Beclin 1 (Becn1), via its evolutionarily conserved domain, STAT3 in major fetal hematopoietic organ mice. Conditional loss Becn1 caused sequential dysfunction and exhaustion liver stem cells, leading to lethal cell-biased hematopoiesis fetus. Molecularly, absence resulted release from tethering subsequent phosphorylation translocation nucleus, which turn directly activated transcription ISG15 coupled increased ISGylation production cytokines, whereas inactivating reduced improved potential, further silencing mitigated above collapse Becn1-null lineage. The Becn1/STAT3/ISG15 axis remains functional autophagy-disrupted organs. These results suggest Becn1, autophagy-independent manner, secures survival fetus by inhibiting STAT3/ISG15 activation prevent cytokine storms. Our findings highlight a previously undocumented role governing safeguard

Language: Английский

Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival DOI Creative Commons
Wen Wei,

Xueqin Gao,

Jiawei Qian

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 135(3)

Published: Nov. 26, 2024

Proper control of inflammatory responses is essential for embryonic development, but the underlying mechanism poorly understood. Here, we show that under physiological conditions, inactivation ISG15, an inflammation amplifier, associated with interaction Beclin 1 (Becn1), via its evolutionarily conserved domain, STAT3 in major fetal hematopoietic organ mice. Conditional loss Becn1 caused sequential dysfunction and exhaustion liver stem cells, leading to lethal cell-biased hematopoiesis fetus. Molecularly, absence resulted release from tethering subsequent phosphorylation translocation nucleus, which turn directly activated transcription ISG15 coupled increased ISGylation production cytokines, whereas inactivating reduced improved potential, further silencing mitigated above collapse Becn1-null lineage. The Becn1/STAT3/ISG15 axis remains functional autophagy-disrupted organs. These results suggest Becn1, autophagy-independent manner, secures survival fetus by inhibiting STAT3/ISG15 activation prevent cytokine storms. Our findings highlight a previously undocumented role governing safeguard

Language: Английский

Citations

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