Hairui Su, Ming Jiang, Chamara Senevirathne, Srinivas Aluri, Tuo Zhang, Han Guo, Juliana Xavier-Ferrucio, Shuiling Jin, Ngoc-Tung Tran, Szu-Mam Liu, Chiao-Wang Sun, Yongxia Zhu, Qing Zhao, Yuling Chen, LouAnn Cable, Yudao Shen, Jing Liu, Cheng-Kui Qu, Xiaosi Han, Christopher A Klug, Ravi Bhatia, Yabing Chen, Stephen D Nimer, Y George Zheng, Camelia Iancu-Rubin, Jian Jin, Haiteng Deng, Diane S Krause, Jenny Xiang, Amit Verma, Minkui Luo, Xinyang Zhao
Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity phosphatases (DUSPs), the activities of which are tightly regulated during cell differentiation. Using knockdown screening and single-cell transcriptional analysis, we demonstrate that DUSP4 is the phosphatase that specifically inactivates p38 kinase to promote megakaryocyte (Mk) differentiation. Mechanistically, PRMT1-mediated methylation of DUSP4 triggers its ubiquitinylation by an E3 ligase HUWE1. Interestingly, the mechanistic axis of the DUSP4 degradation and p38 activation is also associated with a transcriptional signature of immune activation in Mk cells...
July 27, 2021: Cell Reports