Renal cell carcinoma risk in type 2 von Hippel-Lindau disease correlates with defects in pVHL stability and HIF-1alpha interactions.
AuthorsKnauth K, Bex C, Jemth P, Buchberger A,
JournalOncogene
PubMed ID16261165
'The von Hippel-Lindau (VHL) tumor suppressor protein is the substrate binding subunit of the CBC(VHL) E3 ubiquitin ligase complex. Mutations in the VHL gene cause a variety of tumors with complex genotype/phenotype correlations. Type 2A and type 2B VHL disease are characterized by a low or high risk of renal ... More
COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding.
AuthorsMao X, Gluck N, Chen B, Starokadomskyy P, Li H, Maine GN, Burstein E
JournalJ Biol Chem
PubMed ID21778237
'Cullin RING ligases (CRLs), the most prolific class of ubiquitin ligase enzymes, are multimeric complexes that regulate a wide range of cellular processes. CRL activity is regulated by CAND1 (Cullin-associated Nedd8-dissociated protein 1), an inhibitor that promotes the dissociation of substrate receptor components from the CRL. We demonstrate here that ... More
Tumor suppression by the von Hippel-Lindau protein requires phosphorylation of the acidic domain.
AuthorsLolkema MP, Gervais ML, Snijckers CM, Hill RP, Giles RH, Voest EE, Ohh M,
JournalJ Biol Chem
PubMed ID15824109
The tumor suppressor function of the von Hippel-Lindau protein (pVHL) has previously been linked to its role in regulating hypoxia-inducible factor levels. However, VHL gene mutations suggest a hypoxia-inducible factor-independent function for the N-terminal acidic domain in tumor suppression. Here, we report that phosphorylation of the N-terminal acidic domain of ... More
UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1a accumulation.
AuthorsBandau S, Knebel A, Gage ZO, Wood NT, Alexandru G,
JournalBMC Biol
PubMed ID22537386
The proteins from the UBA-UBX family interact with ubiquitylated proteins via their UBA domain and with p97 via their UBX domain, thereby acting as substrate-binding adaptors for the p97 ATPase. In particular, human UBXN7 (also known as UBXD7) mediates p97 interaction with the transcription factor HIF1a that is actively ubiquitylated ... More