Abstract
Imbalanced protein homeostasis (proteostasis) is a driver of aging and a vulnerability for long-lived cells such as hematopoietic stem cells. To determine critical proteostasis factors, we analyzed the proteome of hematopoietic stem and progenitor cells and found prolyl isomerases to be the dominant cytosolic chaperones. Genetic removal of prolyl isomerases led to accelerated aging in the stem cell compartment. We identified intrinsically disordered proteins as common substrates of these chaperones, including several key players that control phase transition. Phase separation allows the formation of supramolecular membrane-less organelles that regulate DNA and RNA biology as well as protein translation. Using microscopy and biochemistry, we show that prolyl isomerases promote phase separation and thereby increase cellular resistance to stress. Our research links a ubiquitously expressed chaperone family to phase transition and identifies macromolecular condensation dynamics as a driver of blood stem cell aging. Disclosures Yellapragada: Novartis: Employment, Other: Spouse Employment ; Celgene: Research Funding; BMS: Research Funding; Takeda: Research Funding.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
