title: Jun activation domain-binding protein 1 negatively regulate p27 kip1 in non-Hodgkin's lymphomas.
abstract: OBJECTIVE
  Recent evidences suggest that Jun activation domain-binding protein 1 (Jab1) specifically interacts with the Cdk inhibitor p27kip1 and induces nuclear export and subsequent degradation of p27kip1. The purpose of this study is to investigate whether Jab1 expression is correlated with p27kip1 level in Non-Hodgkin's Lymphomas(NHLs) and how it influenced the stability of p27kip1, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of NHLs.
  
  
  RESULTS
  Immunohistochemical analysis showed that Jab1 expression was negatively associated with p27kip1 level and significantly associated with unfavorable clinicopathologic variables. Overexpression Jab1 in lymphoma cell lines Jurkat resulted in decreased p27kip1 level and advanced progression from G(1) to S phase of the cell cycle. Subcellular fractionation confirmed Jab1 could lead to nuclear export of p27kip1. Phosphorylation of p27kip1 at Ser10 and Thr157 was significantly increased after Jab1 transient transfected, while Thr187 phosphorylation was decreased. Immunoprecipitation demonstrated that Jab1 overexpression facilitated p27kip1 to dissociate from Cdk2 and associated with Cdk4. Finally, Survival analysis revealed that Jab1 overexpression is significantly associated with overall survival (P = 0.000). When Jab1 and p27kip1 are combined, patients with Jab1(+)/p27kip1(-) revealed poorer overall survival (p = 0.001). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival.
  
  
  METHODS
  Immunohistochemical and/or Western blot analysis was done in 116 cases of NHLs and Jurkat cells.
  
  
  CONCLUSIONS
  These findings suggest that Jab1 protein may contribute to the tumor progression through Jab1-mediated p27kip1 degradation and that control of Jab1 expression is a novel therapeutic target with NHLs.
authors.affiliation: Department of Immunology and Microbiology, Medical College of Nantong University, Nantong, PR China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Fei
authors.forename: Chun
authors.initials: C
authors.lastname: Cheng
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhao
authors.forename: You
authors.initials: Y
authors.lastname: Wang
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D000075686:COP9 Signalosome Complex; D002470:Cell Survival; D003470:Culture Media; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D019169:Jurkat Cells; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000235:genetics / Q000502:physiology*
chemical_list: C436291:CDKN1B protein, human; D003470:Culture Media; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex