Loss of DCAF8 impairs hematopoietic stem cell function with cellular senescence via the DOCK11-CDC42 axis.

ABSTRACT:

Abstract

Hematopoietic stem cells (HSCs) are responsible for sustaining the hematopoietic system throughout life, and their functional decline contributes to hematological disorders and organismal aging. Understanding the molecular mechanisms that govern HSC function is critical for developing interventions for treating and preventing aging-related diseases. Here, we show that DCAF8, a substrate recognition component of Cullin-RING E3 ubiquitin ligases, is highly expressed in HSCs and undergoes a progressive decline with age. Loss of DCAF8 in mice results in impaired function in HSCs, characterized by increased number yet decreased self-renewal capacity, which associates with cellular senescence and elevated DNA damage. Mechanistically, DCAF8 mediates the degradation of dedicator o

SUBMITTER: Xu P 

PROVIDER: S-EPMC12824705 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature