Cyclophilin A supports translation of intrinsically disordered proteins and affects haematopoietic stem cell ageing.

Autor: Maneix L; Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.; Cell and Gene Therapy Program at the Dan L. Duncan Comprehensive Cancer Center, Houston, TX, USA., Iakova P; Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.; Cell and Gene Therapy Program at the Dan L. Duncan Comprehensive Cancer Center, Houston, TX, USA., Lee CG; Department of BioSciences, Rice University, Houston, TX, USA., Moree SE; Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.; Cell and Gene Therapy Program at the Dan L. Duncan Comprehensive Cancer Center, Houston, TX, USA., Lu X; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA., Datar GK; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA., Hill CT; Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Spooner E; Whitehead Institute for Biomedical Research, Cambridge, MA, USA., King JCK; Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.; Cell and Gene Therapy Program at the Dan L. Duncan Comprehensive Cancer Center, Houston, TX, USA., Sykes DB; Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Saez B; Center for Applied Medical Research, Hematology-Oncology Unit, Pamplona, Navarra, Spain., Di Stefano B; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.; Cell and Gene Therapy Program at the Dan L. Duncan Comprehensive Cancer Center, Houston, TX, USA., Chen X; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA., Krause DS; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Sahin E; Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA., Tsai FTF; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.; Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA., Goodell MA; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.; Cell and Gene Therapy Program at the Dan L. Duncan Comprehensive Cancer Center, Houston, TX, USA., Berk BC; Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA., Scadden DT; Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Catic A; Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA. catic@bcm.edu.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA. catic@bcm.edu.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. catic@bcm.edu.; Cell and Gene Therapy Program at the Dan L. Duncan Comprehensive Cancer Center, Houston, TX, USA. catic@bcm.edu.; Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. catic@bcm.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Apr; Vol. 26 (4), pp. 593-603. Date of Electronic Publication: 2024 Mar 29.
DOI: 10.1038/s41556-024-01387-x
Abstrakt: Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. Haematopoietic stem cell ageing is associated with a post-transcriptional decrease in PPIA expression and reduced translation of IDR-rich proteins. Here we link the chaperone PPIA to the synthesis of intrinsically disordered proteins, which indicates that impaired protein interaction networks and macromolecular condensation may be potential determinants of haematopoietic stem cell ageing.
(© 2024. The Author(s).)
Databáze: MEDLINE
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