VHL Human
Description
Product Specs
MGSSHHHHHH SSGLVPRGSH MPRRAENWDE AEVGAEEAGV EEYGPEEDGG EESGAEESGPEESGPEELGA EEEMEAGRPR PVLRSVNSRE PSQVIFCNRS PRVVLPVWLN FDGEPQPYPT LPPGTGRRIH SYRGHLWLFR DAGTHDGLLV NQTELFVPSL NVDGQPIFAN ITLP.
Product Science Overview
The Von Hippel-Lindau protein, often abbreviated as pVHL, is a crucial tumor suppressor protein encoded by the VHL gene in humans. This protein plays a significant role in the regulation of hypoxia-inducible factors (HIFs), which are transcription factors that respond to changes in oxygen levels within the cellular environment. Mutations in the VHL gene are associated with Von Hippel-Lindau disease, a hereditary condition characterized by the development of tumors and cysts in various parts of the body, including the brain, spinal cord, kidneys, and pancreas .
Recombinant human Von Hippel-Lindau protein is typically produced using recombinant DNA technology. The process involves the following steps:
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Gene Cloning: The DNA sequence encoding the human VHL protein is cloned into an expression vector. This vector is designed to facilitate the production of the protein in a host organism, such as Escherichia coli (E. coli).
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Transformation: The expression vector is introduced into the host organism, which then incorporates the vector into its own genetic material.
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Protein Expression: The host organism is cultured under conditions that promote the expression of the VHL protein. This often involves the use of specific inducers that activate the promoter regions of the expression vector.
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Protein Purification: The expressed VHL protein is purified from the host organism using various chromatographic techniques. These techniques may include affinity chromatography, ion exchange chromatography, and size exclusion chromatography.
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Verification and Quality Control: The purity and activity of the recombinant VHL protein are verified using techniques such as SDS-PAGE, mass spectrometry, and functional assays .
The primary function of the Von Hippel-Lindau protein is its role as an E3 ubiquitin ligase. This means that pVHL is involved in the ubiquitination and subsequent degradation of specific target proteins. The most well-known target of pVHL is hypoxia-inducible factor 1-alpha (HIF-1α). Under normal oxygen levels, HIF-1α is hydroxylated on specific proline residues, which allows pVHL to bind to it. This binding leads to the ubiquitination of HIF-1α, marking it for degradation by the proteasome .
During hypoxic conditions, the proline residues on HIF-1α are not hydroxylated, preventing pVHL from binding to it. As a result, HIF-1α accumulates and activates the transcription of genes involved in angiogenesis, erythropoiesis, and glycolysis. This regulatory mechanism is crucial for cellular adaptation to low oxygen levels .
In the context of Von Hippel-Lindau disease, mutations in the VHL gene often disrupt the ability of pVHL to bind to HIF-1α, leading to the stabilization and accumulation of HIF-1α even under normal oxygen conditions. This aberrant activation of HIF-1α contributes to the development of tumors and cysts characteristic of the disease .
