title: TAK1 promotes cell survival by TNFAIP3 and IL-8 dependent and NF-κB independent pathway in HeLa cells exposed to heat stress.
abstract: OBJECTIVE
  Transforming growth factor-β-activated kinase 1 (TAK1) plays a role in inhibiting apoptosis in response to multiple stresses. In the present study, we investigated the role of TAK1 in cell death induced by heat stress (HS).
  
  
  METHODS
  TAK1 knockdown HeLa cells and their parental cells were exposed to HS at 44 °C for 15, 30, 45 min followed by colony formation assay. Heat shock proteins (HSPs) induction, NF-κB phosphorylation, and caspase-3 cleavage were estimated by western blotting using specific antibodies. Global gene expression analysis was performed using the GeneChip® system. The anti-apoptotic roles of the identified genes were elucidated using small interfering RNAs targeting those genes.
  
  
  RESULTS
  Heat sensitivity estimated by colony formation assay and caspase-3 cleavage increased in TAK1 knockdown cells. This sensitisation was not due to alterations in HSP induction or NF-κB phosphorylation as the expression levels of these proteins did not differ significantly between the TAK1 knockdown and the parent cells after HS exposure. The GeneChip® analysis revealed differences in gene expression between both cell variants after HS exposure and defined the genetic network associated with cell death. TNF-α interacting protein 3 (TNFAIP3) and Interleukin 8 (IL-8) are two of the identified genes. RNA interference against these genes increased the cleavage of caspase-3 and cell death after HS exposure.
  
  
  CONCLUSIONS
  Our findings reveal the role of TAK1 in thermoresistance and show that the mediation is independent of NF-κB phosphorylation but is dependent on TNFAIP3 and IL-8 induction.
authors.affiliation: Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani , Toyama , Japan .
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Zheng-Li
authors.initials: ZL
authors.lastname: Wei
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Zhao
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D000099151:MAP Kinase Kinase Kinase 7; C508606:CXCL8 protein, human; C076529:TNFAIP3 protein, human