Chen K, Chen S, Huang C, Cheng H, Zhou R

BACKGROUND INFORMATION: The translationally controlled tumor protein (TCTP) plays an important role in maintaining cell proliferation and its high expression is associated with many tumors. The tumor suppressor von Hippel-Lindau protein (VHL) has been shown to function as an E3 ubiquitin ligase. Although great progress has been made, biological roles ...

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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 overexpression 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 overexpression 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 VEGF (vascular endothelial growth factor)-HRE (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.

Date: Feb. 06, 2013

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