title: CRIF1 interacting with CDK2 regulates bone marrow microenvironment-induced G0/G1 arrest of leukemia cells.
abstract: BACKGROUND
  To assess the level of CR6-interacting factor 1 (CRIF1), a cell cycle negative regulator, in patients with leukemia and investigate the role of CRIF1 in regulating leukemia cell cycle.
  
  
  METHODS
  We compared the CRIF1 level in bone marrow (BM) samples from healthy and acute myeloid leukemia (AML), iron deficiency anemia (IDA) and AML-complete remission (AML-CR) subjects. We also manipulated CRIF1 level in the Jurkat cells using lentivirus-mediated overexpression or siRNA-mediated depletion. Co-culture with the BM stromal cells (BMSCs) was used to induce leukemia cell cycle arrest and mimic the BM microenvironment.
  
  
  RESULTS
  We found significant decreases of CRIF1 mRNA and protein in the AML group. CRIF1 overexpression increased the proportion of Jurkat cells arrested in G0/G1, while depletion of endogenous CRIF1 decreased cell cycle arrest. Depletion of CRIF1 reversed BMSCs induced cell cycle arrest in leukemia cells. Co-immunoprecipitation showed a specific binding of CDK2 to CRIF1 in Jurkat cells during cell cycle arrest. Co-localization of two proteins in both nucleus and cytoplasm was also observed with immunofluorescent staining.
  
  
  CONCLUSIONS
  CRIF1 may play a regulatory role in the BM microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor.
authors: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Qian
authors: Q
authors: Ran
authors: Oncologic Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Ping
authors: P
authors: Hao
authors: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Yanni
authors: Y
authors: Xiao
authors: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Lixing
authors: L
authors: Xiang
authors: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Xingde
authors: X
authors: Ye
authors: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Xiaojun
authors: X
authors: Deng
authors: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Jiang
authors: J
authors: Zhao
authors: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Zhongjun
authors: Z
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000378:metabolism*; D060833:Cellular Microenvironment; D002648:Child; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D042541:Intracellular Space; D019169:Jurkat Cells; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C476586:GADD45GIP1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2