Tid-1 interacts with the von Hippel-Lindau protein and modulates angiogenesis by destabilization of HIF-1alpha.

نویسندگان

  • Moon-Kyoung Bae
  • Joo-Won Jeong
  • Se-Hee Kim
  • Soo-Young Kim
  • Hye Jin Kang
  • Dong-Min Kim
  • Soo-Kyung Bae
  • Il Yun
  • Grace A Trentin
  • Maria Rozakis-Adcock
  • Kyu-Won Kim
چکیده

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.

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عنوان ژورنال:
  • Cancer research

دوره 65 7  شماره 

صفحات  -

تاریخ انتشار 2005