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Modulation of Protein Stability: Targeting the VHL Pathway

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Modulation of Protein Stability in Cancer Therapy

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Abstract

Inactivation of the von Hippel–Lindau tumor suppressor protein (pVHL) has been linked to a variety of tumors such as renal cell carcinoma, pheochromocytomas, and cerebellar hemangioblastomas. The best characterized of its many proposed functions is the ability to downregulate hypoxia-inducible factor-α (HIFα) subunits. Inactivation of pVHL and its ubiquitin ligase activity result in the stabilization of HIFα subunits and the transactivation of HIF target genes. Therapeutic approaches that restore pVHL action or inhibit HIF transcriptional activity remain unrealized and will likely remain a therapeutic challenge. Several pVHL independent pathways that alter HIFα protein stability have recently been identified, and the availability of inhibitors in clinical trials makes these pathways attractive for further investigation.

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA

    William Y. Kim & William G. Kaelin Jr.

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  1. William Y. Kim
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  2. William G. Kaelin Jr.
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Correspondence to William G. Kaelin Jr. .

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Eric Rubin Kathleen Sakamoto

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Kim, W.Y., Kaelin, W.G. (2009). Modulation of Protein Stability: Targeting the VHL Pathway. In: Rubin, E., Sakamoto, K. (eds) Modulation of Protein Stability in Cancer Therapy. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69147-3_4

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