Induction of the Mdm2 gene and protein by kinase signaling pathways is repressed by the pVHL tumor suppressor.
Mdm2
p53
pVHL
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
30 Jul 2024
30 Jul 2024
Historique:
medline:
26
7
2024
pubmed:
26
7
2024
entrez:
24
7
2024
Statut:
ppublish
Résumé
The tumor suppressor von Hippel-Lindau, pVHL, is a multifaceted protein. One function is to dock to the hypoxia-inducible transcription factor (HIF) and recruit a larger protein complex that destabilizes HIF via ubiquitination, preventing angiogenesis and tumor development. pVHL also binds to the tumor suppressor p53 to activate specific p53 target genes. The oncogene Mdm2 impairs the formation of the p53-pVHL complex and activation of downstream genes by conjugating nedd8 to pVHL. While Mdm2 can impact p53 and pVHL, how pVHL may impact Mdm2 is unclear. Like p53 somatic mutations, point mutations are evident in pVHL that are common in renal clear cell carcinomas (RCC). In patients with RCC, Mdm2 levels are elevated, and we examined whether there was a relationship between Mdm2 and pVHL. TCGA and DepMap analysis revealed that
Identifiants
pubmed: 39047034
doi: 10.1073/pnas.2400935121
doi:
Substances chimiques
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Von Hippel-Lindau Tumor Suppressor Protein
EC 2.3.2.27
VHL protein, human
EC 6.3.2.-
MDM2 protein, human
EC 2.3.2.27
Tumor Suppressor Protein p53
0
TP53 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2400935121Subventions
Organisme : Riley Children's Foundation (RCF)
ID : Internal
Déclaration de conflit d'intérêts
Competing interests statement:The authors declare no competing interest.