PUBLICATION
Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage
- Authors
- Zhang, X., Ge, L., Jin, G., Liu, Y., Yu, Q., Chen, W., Chen, L., Dong, T., Miyagishima, K.J., Shen, J., Yang, J., Lv, G., Xu, Y., Yang, Q., Ye, L., Yi, S., Li, H., Zhang, Q., Chen, G., Liu, W., Yang, Y., Li, W., Ou, J.
- ID
- ZDB-PUB-240404-16
- Date
- 2024
- Source
- Nature communications 15: 28592859 (Journal)
- Registered Authors
- Liu, Wei
- Keywords
- none
- MeSH Terms
-
- Active Transport, Cell Nucleus
- Animals
- Diabetes Mellitus, Experimental*
- Forkhead Box Protein O1/genetics
- Forkhead Box Protein O1/metabolism
- Forkhead Transcription Factors*/genetics
- Forkhead Transcription Factors*/metabolism
- Humans
- Karyopherins/metabolism
- Mice
- Zebrafish/metabolism
- PubMed
- 38570500 Full text @ Nat. Commun.
Citation
Zhang, X., Ge, L., Jin, G., Liu, Y., Yu, Q., Chen, W., Chen, L., Dong, T., Miyagishima, K.J., Shen, J., Yang, J., Lv, G., Xu, Y., Yang, Q., Ye, L., Yi, S., Li, H., Zhang, Q., Chen, G., Liu, W., Yang, Y., Li, W., Ou, J. (2024) Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage. Nature communications. 15:28592859.
Abstract
Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping