What question did this study set out to answer?

To determine how the molecular chaperone Hsp90 regulates HIF-1α stability and transcriptional activity in von Hippel-Lindau-deficient renal carcinoma cells.

August 1, 2002Journal of Biological ChemistryOpen Access

Hsp90 Regulates a von Hippel Lindau-independent Hypoxia-inducible Factor-1α-degradative Pathway

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Authors

JIJennifer S. IsaacsUniversity of Kentucky YJYunjin JungPusan National University EMEdward G. MimnaughNational Institutes of Health

Discussion

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Overview

In vitro study demonstrates that Hsp90 inhibition drives VHL-independent HIF-1α proteasomal degradation in renal carcinoma cells, suggesting a strategy to target hypoxic tumor angiogenesis.

Key Points

To determine how the molecular chaperone Hsp90 regulates HIF-1α stability and transcriptional activity in von Hippel-Lindau-deficient renal carcinoma cells.
Treated VHL-deficient renal carcinoma cell lines with the Hsp90 antagonist geldanamycin under normoxic and hypoxic conditions.
Evaluated HIF-1α protein degradation, ubiquitination, and the impact of HIF-1α point mutations that prevent VHL binding.
Assessed HIF-1α-driven transcriptional activity, VEGF mRNA expression, and hypoxia-dependent angiogenic activity.
Geldanamycin triggered rapid ubiquitination and proteasomal degradation of HIF-1α in renal carcinoma cells under both normoxia and hypoxia, bypassing the need for functional VHL.
Point mutations that prevent HIF-1α from binding VHL did not protect the protein from geldanamycin-induced degradation.
Hsp90 inhibition significantly suppressed HIF-1α transcriptional activity, markedly reducing hypoxia-induced VEGF mRNA accumulation and downstream angiogenic activity.

Cite This Study

Isaacs et al. (2002) studied this question.

synapsesocial.com/papers/6a02af70daa0ebdf9f9e2bf9 https://doi.org/10.1074/jbc.m204733200

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August 1, 2002Journal of Biological ChemistryOpen Access

Hsp90 Regulates a von Hippel Lindau-independent Hypoxia-inducible Factor-1α-degradative Pathway

View Full Paper

Ask AI

Bookmark

Authors

JIJennifer S. IsaacsUniversity of Kentucky YJYunjin JungPusan National University EMEdward G. MimnaughNational Institutes of Health

Discussion

Member takes

Overview

In vitro study demonstrates that Hsp90 inhibition drives VHL-independent HIF-1α proteasomal degradation in renal carcinoma cells, suggesting a strategy to target hypoxic tumor angiogenesis.

Key Points

To determine how the molecular chaperone Hsp90 regulates HIF-1α stability and transcriptional activity in von Hippel-Lindau-deficient renal carcinoma cells.
Treated VHL-deficient renal carcinoma cell lines with the Hsp90 antagonist geldanamycin under normoxic and hypoxic conditions.
Evaluated HIF-1α protein degradation, ubiquitination, and the impact of HIF-1α point mutations that prevent VHL binding.
Assessed HIF-1α-driven transcriptional activity, VEGF mRNA expression, and hypoxia-dependent angiogenic activity.
Geldanamycin triggered rapid ubiquitination and proteasomal degradation of HIF-1α in renal carcinoma cells under both normoxia and hypoxia, bypassing the need for functional VHL.
Point mutations that prevent HIF-1α from binding VHL did not protect the protein from geldanamycin-induced degradation.
Hsp90 inhibition significantly suppressed HIF-1α transcriptional activity, markedly reducing hypoxia-induced VEGF mRNA accumulation and downstream angiogenic activity.

Cite This Study

Isaacs et al. (2002) studied this question.

synapsesocial.com/papers/6a02af70daa0ebdf9f9e2bf9 https://doi.org/10.1074/jbc.m204733200

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