DCAF13 Safeguards Hematopoietic Stem Cells via RRS1-Regulated Ribosome Biogenesis - PubMed
4 days ago
- #DCAF13-RRS1 Axis
- #Hematopoietic Stem Cells
- #Ribosome Biogenesis
- DCAF13 is identified as a critical regulator of hematopoietic stem cell (HSC) maintenance by stabilizing RRS1, a key factor in ribosome biogenesis.
- Conditional deletion of Dcaf13 in murine hematopoietic cells leads to severe pancytopenia, rapid mortality, and complete HSC depletion in both fetal and adult hematopoietic compartments.
- DCAF13 deficiency disrupts ribosome assembly and protein synthesis, selectively affecting the translation of mRNAs involved in myeloid differentiation, chromatin remodeling, and erythroid homeostasis.
- DCAF13 directly binds RRS1 and catalyzes its K27-linked polyubiquitination, enhancing RRS1 protein stability.
- Dcaf13 deletion activates the p53 pathway, but Trp53 ablation only partially restores HSC numbers and cell cycle progression, indicating both p53-dependent and p53-independent mechanisms are involved.
- The findings establish a DCAF13-RRS1 axis essential for HSC function, providing insights into the pathogenesis of hematopoietic disorders and ribosomopathies.