Gain of function mutant p53 protein activates AKT through the Rac1 signaling to promote tumorigenesis.
Breast Neoplasms
/ genetics
Carcinogenesis
/ genetics
Cell Proliferation
/ genetics
Cohort Studies
Enzyme Activation
Female
Gain of Function Mutation
/ genetics
Humans
Mutant Proteins
/ metabolism
Phosphorylation
Protein Binding
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
Sumoylation
Tumor Suppressor Protein p53
/ genetics
rac1 GTP-Binding Protein
/ antagonists & inhibitors
ras GTPase-Activating Proteins
/ metabolism
AKT
Mutant p53
Rac1
gain of function
tumorigenesis
Journal
Cell cycle (Georgetown, Tex.)
ISSN: 1551-4005
Titre abrégé: Cell Cycle
Pays: United States
ID NLM: 101137841
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
pubmed:
11
4
2020
medline:
27
8
2021
entrez:
11
4
2020
Statut:
ppublish
Résumé
Tumor suppressor p53 is the most frequently mutated gene in human cancer. Mutant p53 (mutp53) not only loses the tumor suppressive activity of wild type p53, but often gains new oncogenic activities to promote tumorigenesis, defined as mutp53 gain of function (GOF). While the concept of mutp53 GOF is well-established, its underlying mechanism is not well-understood. AKT has been suggested to be activated by mutp53 and contribute to mutp53 GOF, but its underlying mechanism is unclear. In this study, we found that the activation of the Rac1 signaling by mutp53 mediates the promoting effect of mutp53 on AKT activation. Blocking Rac1 signaling by RNAi or a Rac1 inhibitor can inhibit AKT activation by mutp53. Importantly, targeting Rac1/AKT can greatly compromise mutp53 GOF in tumorigenesis. Results from this study uncover a new mechanism for AKT activation in tumors, and reveal that activation of AKT by mutp53
Identifiants
pubmed: 32275841
doi: 10.1080/15384101.2020.1749790
pmc: PMC7469461
doi:
Substances chimiques
DAB2IP protein, human
0
Mutant Proteins
0
Tumor Suppressor Protein p53
0
ras GTPase-Activating Proteins
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
rac1 GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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