VHL (von Hippel-Lindau disease tumor suppressor) is a component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent degradation of targeted proteins []. Human VHL has been demonstrated to form a ternary complex with elonginB and elonginC proteins []. This complex binds Cul2, which then is involved in regulation of vascular endothelial growth factor mRNA. VHL appears to act as the target recruitment subunit in the E3 ubiquitin ligase complex and recruit hydroxylated hypoxia-inducible factor (HIF) under normal oxygen conditions []. VHL is also involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases []. Like human VHL, Drosophila VHL complex containing Cul-2, Rbx1, Elongins B and C, exhibits E3 ubiquitin ligase activity []. However, proteins in this entry also include Von Hippel-Lindau-like (VHLL) protein from human. It may has little or no E3 ubiquitin ligase activity as it lacks the alpha domain required for nucleating the multiprotein E3 ubiquitin ligase complex [].
von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B [, , , , , , , , , , , , , ,, , , , , ].Von Hippel-Lindau disease tumor suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in beta sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain, interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain, and significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL [].
Elongin B is a subunit of the transcription factor B (SIII) complex, which activates elongation by mammalian RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin is a heterotrimer composed of A, B, and C subunits. Elongin A functions as the transcriptionally active component of Elongin (SIII), while Elongin B and C are regulatory subunits [].Elongin B has been shown to form complex with Elongin C and VHL (von Hippel-Lindau, a tumour suppressor). This complex, known as the VBC complex, shows structural similarities with the SCF complex []. The VBC complex binds to hypoxia-inducible factor 1alpha (HIF-1alpha) via VHL and targets HIF-1alpha for ubiquitination [].
Prefoldin subunit 3 (PFD3, also known as VBP-1) is part of the heteromeric co-chaperone complex, which delivers unfolded proteins to cytosolic chaperonin and acts as a cofactor. PFD3 binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. It binds to nascent polypeptide chain and promotes folding []. In fruit flies PFD3 (also known as mgr) interacts with von Hippel Lindau protein (Vhl) and betaTub56D/tubulin beta-1 chain. It is required for tubulin stability and spindle and centrosome formation in cooperation with Vhl [].
von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitinligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B [, , , , , , , , , , , , , , , , , , , ].Von Hippel-Lindau disease tumor suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in beta sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain, interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain, and significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL [].This entry represents the beta domain of VHL.
von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B [, , , , , , , , , , , , , , , , , , , ].Von Hippel-Lindau disease tumor suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in beta sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain, interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain, and significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL [].This entry represents the alpha domain of VHL.
von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B [, , , , , , , , , , , , , , , , , , , ].Von Hippel-Lindau disease tumor suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in beta sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain, interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain, and significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL [].This entry represents both beta and alpha domains of VHL.
von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B [, , , , , , , , , , , , , , , , , , , ].Von Hippel-Lindau disease tumor suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in beta sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain, interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain, and significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL [].This entry represents the beta domain superfamily of VHL.
von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologs are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterized putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF independent cellular processes. Germline VHL mutations cause renal cell carcinomas, hemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilize microtubules and foster the maintenance of primary cilium. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B [, , , , , , , , , , , , , , , , , , , ].Von Hippel-Lindau disease tumor suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in beta sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain, interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain, and significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL [].This entry represents the alpha domain superfamily of VHL.
