p53-Pirh2 Complex Promotes Twist1 Degradation and Inhibits EMT.
Cell Line, Tumor
Cystadenocarcinoma, Serous
/ genetics
Epithelial-Mesenchymal Transition
Female
HEK293 Cells
Humans
Mutation
Nuclear Proteins
/ biosynthesis
Ovarian Neoplasms
/ genetics
Proteasome Endopeptidase Complex
/ metabolism
Tumor Suppressor Protein p53
/ deficiency
Twist-Related Protein 1
/ biosynthesis
Ubiquitin-Protein Ligases
/ genetics
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
09
03
2018
revised:
29
06
2018
accepted:
03
08
2018
pubmed:
23
8
2018
medline:
24
1
2020
entrez:
23
8
2018
Statut:
ppublish
Résumé
Epithelial-mesenchymal transition (EMT) is a critical process involved in cancer metastasis and chemoresistance. Twist1 is a key EMT-inducing transcription factor, which is upregulated in multiple types of cancers and has been shown to promote tumor cell invasiveness and support tumor progression. Conversely, p53 is a tumor suppressor gene that is frequently mutated in cancers. This study demonstrates the ability of wild-type (WT) p53 to promote the degradation of Twist1 protein. By forming a complex with Twist1 and the E3 ligase Pirh2, WT p53 promotes the ubiquitination and proteasomal degradation of Twist1, thus inhibiting EMT and maintaining the epithelial phenotype. The ability of p53 to induce Twist1 degradation is abrogated when p53 is mutated. Consequently, the loss of p53-induced Twist1 degradation leads to EMT and the acquisition of a more invasive cancer phenotype.
Identifiants
pubmed: 30131448
pii: 1541-7786.MCR-18-0238
doi: 10.1158/1541-7786.MCR-18-0238
pmc: PMC6800184
mid: NIHMS1019194
doi:
Substances chimiques
Nuclear Proteins
0
TP53 protein, human
0
TWIST1 protein, human
0
Tumor Suppressor Protein p53
0
Twist-Related Protein 1
0
RCHY1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
153-164Subventions
Organisme : NCI NIH HHS
ID : R01 CA199004
Pays : United States
Informations de copyright
©2018 American Association for Cancer Research.
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