title: TCTP increases stability of hypoxia-inducible factor 1α by interaction with and degradation of the tumour suppressor VHL.
abstract: BACKGROUND
  The translationally controlled tumour protein (TCTP) plays an important role in maintaining cell proliferation and its high expression is associated with many tumours. The tumour suppressor von Hippel-Lindau protein (VHL) has been shown to function as an E3 ubiquitin ligase. Although great progress has been made, biological roles of these factors and relevant molecular mechanisms remain largely unknown.
  
  
  RESULTS
  In this study, we have shown that TCTP specifically binds to VHL through its β domain and competes with hypoxia-inducible factor-1α (HIF1α). TCTP over-expression decreased the protein level of VHL and the inhibition of TCTP expression by miRNA resulted in an increase of the VHL protein level. Moreover, TCTP over-expression promoted the K48-linked ubiquitination of VHL, thus degradation through the ubiquitin-proteasome pathway. In addition, we showed that TCTP increased the protein level of HIF1α, which promoted both vascular endothelial growth factor-hypoxic response element-promoter-driven luciferase reporter and endogenous VEGF expression.
  
  
  CONCLUSIONS
  These data have demonstrated that TCTP binds to the β domain of VHL through competition with HIF1α, which promotes VHL degradation by the ubiquitin-proteasome system and HIF1α stability.
authors: Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Ke
authors: K
authors: Chen
authors: Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Shuliang
authors: S
authors: Chen
authors: Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Chunhua
authors: C
authors: Huang
authors: Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Hanhua
authors: H
authors: Cheng
authors: Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Rongjia
authors: R
authors: Zhou
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D055550:Protein Stability; D059748:Proteolysis; D015533:Transcriptional Activation; D000090324:Tumor Protein, Translationally-Controlled 1; D054875:Ubiquitination; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D046988:Proteasome Endopeptidase Complex; C497446:VHL protein, human