Tid-1 interacts with the von Hippel-Lindau protein and modulates angiogenesis by destabilization of HIF-1alpha.
The von Hippel-Lindau protein (pVHL) is a major tumor suppressor protein and also associated with the inhibition of angiogenesis via HIF-1alpha ubiquitination and proteasomal degradation. To further elucidate the biological activity of pVHL in angiogenesis, pVHL-interacting proteins were screened using the yeast two-hybrid system. We found that a mouse homologue ... of the long form of Drosophila tumor suppressor l(2)tid, Tid-1(L), directly interacts with pVHL in vitro and in vivo. Furthermore, Tid-1(L) protein; enhanced the interaction between HIF-1alpha and pVHL, leading to the destabilization of HIF-1alpha protein; therefore, Tid-1(L) protein decreased vascular endothelial growth factor expression and inhibited angiogenesis in vivo and in vitro. These findings propose that Tid-1(L) may play a critical role in pVHL-mediated tumor suppression by modulating the pVHL-dependent HIF-1alpha stability.
Mesh Terms:
Chorioallantoic Membrane, Down-Regulation, Endothelial Cells, HSP40 Heat-Shock Proteins, Heat-Shock Proteins, Hela Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Neovascularization, Physiologic, Plasmids, RNA, Messenger, Transcription Factors, Transfection, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases, Vascular Endothelial Growth Factor A, Von Hippel-Lindau Tumor Suppressor Protein
Chorioallantoic Membrane, Down-Regulation, Endothelial Cells, HSP40 Heat-Shock Proteins, Heat-Shock Proteins, Hela Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Neovascularization, Physiologic, Plasmids, RNA, Messenger, Transcription Factors, Transfection, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases, Vascular Endothelial Growth Factor A, Von Hippel-Lindau Tumor Suppressor Protein
Cancer Res.
Date: Apr. 01, 2005
PubMed ID: 15805242
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