title: CHIP functions an E3 ubiquitin ligase of Runx1.
abstract: Runx1 is a key factor in the generation and maintenance of hematopoietic stem cells. Improper expression and mutations in Runx1 are frequently implicated in human leukemia. Here, we report that CHIP, the carboxyl terminus of Hsc70-interacting protein, also named Stub1, physically interacts with Runx1 through the TPR and Charged domains in the nucleus. Over-expression of CHIP directly induced Runx1 ubiquitination and degradation through the ubiquitin-proteasome pathway. Interestingly, we found that CHIP-mediated degradation of Runx1 is independent of the molecular chaperone Hsp70/90. Taken together, we propose that CHIP serves as an E3 ubiquitin ligase that regulates Runx1 protein stability via an ubiquitination and degradation mechanism that is independent of Hsp70/90.
authors.affiliation: School of Medicine, Department of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shang
authors.forename: Xinghui
authors.initials: X
authors.lastname: Zhao
authors.forename: Xialian
authors.initials: X
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.forename: Xueni
authors.initials: X
authors.lastname: Li
authors.forename: Yonggong
authors.initials: Y
authors.lastname: Zhai
authors.forename: Dacheng
authors.initials: D
authors.lastname: He
authors.forename: Baoqing
authors.initials: B
authors.lastname: Jia
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
mesh_terms: D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C493728:RUNX1 protein, human; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases