Huan Liu, Lu Sun, Hongfei Zhao, Zihan Zhao, Shiyue Zhang, Shan Jiang, Tianran Cheng, Xiaohan Wang, Tong Wang, Ya Shao, Haiyan Zhu, Huijuan Han, Yigeng Cao, Erlie Jiang, Yihai Cao, Yuanfu Xu
Hematopoietic stem and progenitor cells (HSPCs) that have impaired differentiation can transform into leukemic blasts. However, the mechanism that controls differentiation remains elusive. Here, we show that the genetic elimination of Proteinase 3 (PRTN3) in mice led to spontaneous myeloid differentiation. Mechanistically, our findings indicate that PRTN3 interacts with the N-terminal of STAT3, serving as a negative regulator of STAT3-dependent myeloid differentiation. Specifically, PRTN3 promotes STAT3 ubiquitination and degradation, while simultaneously reducing STAT3 phosphorylation and nuclear translocation during G-CSF-stimulated myeloid differentiation...
April 8, 2024: Cell Death and Differentiation