An important von Hippel-Lindau tumor suppressor domain mediates Sp1-binding and self-association

Herbert T. Cohen, Mi Zhou, Adam M. Welsh, Sharzad Zarghamee, Holger Scholz, Debabrata Mukhopadhyay, Takeshi Kishida, Berton Zbar, Bertrand Knebelmann, Vikas P. Sukhatme

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


VHL is the causative gene for both von Hippel-Lindau (VHL) disease and sporadic clear-cell renal cancer. We showed earlier that VHL downregulates vascular endothelial growth factor transcription by directly binding and inhibiting the transcriptional activator Sp1. We have now mapped the VHL Sp1-binding domain to amino acids 96-122. The 96-122 domain is disproportionately affected by substitution mutations, which interfere with the VHL-Sp1 interaction. Deletion of the 96-122 domain prevents VHL effects on Sp1 DNA binding and on VHL target gene expression, indicating the domain contributes importantly to VHL tumor suppressor activity. Nevertheless, prevention of the VHL-Sp1 interaction only partially abrogates VHL's transcriptional repressor activity, supporting the existence of VHL transcriptional effecters in addition to Sp1. VHL also directly interacts with the Sp1 zinc fingers and self-associates via the 96-122 domain, which furthermore suggest the domain may bind other metalloproteins and contribute to VHL dominant-negative effects.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Dec 9 1999

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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