Premium
TCTP increases stability of hypoxia‐inducible factor 1α by interaction with and degradation of the tumour suppressor VHL
Author(s) -
Chen Ke,
Chen Shuliang,
Huang Chunhua,
Cheng Hanhua,
Zhou Rongjia
Publication year - 2013
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.201200080
Subject(s) - ubiquitin ligase , ubiquitin , biology , proteasome , hypoxia inducible factors , suppressor , protein degradation , luciferase , microbiology and biotechnology , transcription factor , cancer research , cell culture , biochemistry , transfection , gene , genetics
Background Information 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.