title: β-Arrestin1 promotes the progression of chronic myeloid leukaemia by regulating BCR/ABL H4 acetylation.
abstract: BACKGROUND
  β-Arrestins are scaffold proteins that interact with various cellular signals. Although β-arrestin2 mediates the initiation and progression of myeloid leukaemia, the critical role of β-arrestin1 in the chronic myeloid leukaemia (CML) is still unknown. The aim of this study is to investigate the essential function of β-arrestin1 in CML.
  
  
  METHODS
  The expressions of β-arrestin1 and BCR/ABL in CML patients, animal models and K562 cells were measured by RT-PCR, immunofluorescence and western blotting. The effect of β-arrestin1 on CML animal models and K562 cells by colony formation, MTT and survival analysis were assessed. BCR/ABL H4 acetylation was analysed through the use of Chromatin-immunoprecipitation (ChIP) -on-chip and confirmed by ChIP respectively. Co-immunoprecipitation and confocal were examined for the binding of β-arrestin1 with enhancer of zeste homologue 2 (EZH2).
  
  
  RESULTS
  The higher expression of β-arrestin1 is positively correlated with clinical phases of CML patients. Depletion of β-arrestin1 decelerates progression of K562 and primary cells, and increases survival of CML mice. Importantly, silenced β-arrestin1 results in the decrease of BCR/ABL H4 acetylation level in K562 cells. Further data illustrate that nuclear β-arrestin1 binds to EZH2 to mediate BCR/ABL acetylation and thus regulates cell progression in K562 cells and the survival of CML mice.
  
  
  CONCLUSIONS
  Our findings reveal a novel function of β-arrestin1 binding to EZH2 to promote CML progression by regulating BCR/ABL H4 acetylation.
authors.affiliation: 1] Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [2] Department of Laboratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [3] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [4] Key Laboratory of Pediatrics in Chongqing, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
authors.forename: R
authors.initials: R
authors.lastname: Qin
authors.affiliation: 1] Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [2] Department of Laboratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [3] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [4] Key Laboratory of Pediatrics in Chongqing, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.affiliation: 1] Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [2] Department of Laboratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [3] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [4] Key Laboratory of Pediatrics in Chongqing, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
authors.forename: X
authors.initials: X
authors.lastname: Qi
authors.affiliation: 1] Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [2] Department of Laboratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [3] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [4] Key Laboratory of Pediatrics in Chongqing, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Chongqing Stem Cell Therapy Engineering Technique Center, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1] Department of Laboratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [2] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [3] Key Laboratory of Pediatrics in Chongqing, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [4] Hematological Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 1] Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [2] Department of Laboratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [3] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing 400014, China [4] Key Laboratory of Pediatrics in Chongqing, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
authors.forename: L
authors.initials: L
authors.lastname: Zou
mesh_terms: D000107:Acetylation; D000328:Adult; D000818:Animals; D019390:Arrestins / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055815:Young Adult; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D006657:Histones; D000071557:beta-Arrestins; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D016044:Fusion Proteins, bcr-abl