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The CKS1/CKS2 proteostasis axis is crucial to maintain hematopoietic stem cell function

ABSTRACT: Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification and degradation – broadly termed protein homeostasis or “proteostasis” – in these cells is still in its infancy. Here we report the requirement of the small phospho-binding adaptor proteins, the cyclin dependent kinase subunits (Cks1 and Cks2), for maintaining ordered hematopoiesis and long-term hematopoietic stem cell reconstitution. Cks1 and Cks2 are critical regulators of a myriad of key intracellular signalling pathways that govern hematopoietic stem cell biology and together they balance protein homeostasis and restrain reactive oxygen species to ensure healthy hematopoietic stem cell function.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Cell, Haematopoietic Stem Cells

SUBMITTER: Pedro Casado-Izquierdo

LAB HEAD: Pedro R. Cutillas

PROVIDER: PXD035984 | Pride | 2023-03-11

REPOSITORIES: Pride

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The CKS1/CKS2 Proteostasis Axis Is Crucial to Maintain Hematopoietic Stem Cell Function.

Grey William W Atkinson Samantha S Rix Beatrice B Casado Pedro P Ariza-McNaughton Linda L Hawley Cathy C Sopoena Miriam L ML Bridge Katherine S KS Kent David D Cutillas Pedro R PR Bonnet Dominique D

HemaSphere 20230228 3

Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic, and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification, and degradation-broadly termed protein homeostasis or "proteostasi ...[more]

PMID: 36874381

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