2021
DOI: 10.1038/s41467-021-20928-8
|View full text |Cite
|
Sign up to set email alerts
|

The oncogenicity of tumor-derived mutant p53 is enhanced by the recruitment of PLK3

Abstract: Abstractp53 mutations with single amino acid changes in cancer often lead to dominant oncogenic changes. Here, we have developed a mouse model of gain-of-function (GOF) p53-driven lung cancer utilizing conditionally active LSL p53-R172H and LSL K-Ras-G12D knock-in alleles that can be activated by Cre in lung club cells. Mutation of the p53 transactivation domain (TAD) (p53-L25Q/W26S/R172H) eliminating significant transactivation activity resulted in loss of tumorigenicity, demonstrating that transactivation me… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
4
1

Citation Types

0
12
0

Year Published

2022
2022
2024
2024

Publication Types

Select...
9

Relationship

0
9

Authors

Journals

citations
Cited by 16 publications
(12 citation statements)
references
References 71 publications
0
12
0
Order By: Relevance
“…Among the SMGs, TP53 mutation was the most frequent variant. It was the shared node in p53 , Wnt / β-Catenin , and the DNA-repair pathway, indicating that multiple oncogenic pathways co-exist and function simultaneously in most HAS patients, which might promote tumorigenesis and invasion of HAS [ 22 , 23 ]. Additionally, six of the SMGs were more highly mutated in HAS than in both LIHC and GC, including PHLDA1 , GMEB2 , CCDC15 , PTH2 , NFYA , and C2orf44 .…”
Section: Discussionmentioning
confidence: 99%
“…Among the SMGs, TP53 mutation was the most frequent variant. It was the shared node in p53 , Wnt / β-Catenin , and the DNA-repair pathway, indicating that multiple oncogenic pathways co-exist and function simultaneously in most HAS patients, which might promote tumorigenesis and invasion of HAS [ 22 , 23 ]. Additionally, six of the SMGs were more highly mutated in HAS than in both LIHC and GC, including PHLDA1 , GMEB2 , CCDC15 , PTH2 , NFYA , and C2orf44 .…”
Section: Discussionmentioning
confidence: 99%
“…Recent studies have found that inhibition of ATM, AURKB, and PLK3 can inhibit the invasion, metastasis, and drug resistance of LC. [44][45][46] However, the role of PRKCQ in LU has not been found. miRNAs are a class of non-coding RNAs that play an essential role in the regulation of gene expression.…”
Section: Discussionmentioning
confidence: 99%
“…Polo-like kinases (including PLK3 ) are a family of 5 serine/threonine kinases that play an essential role in cell cycle, mitotic entry, DNA replication and stress response ( 32 ). Various mechanisms have been described for PLK3 ’s potential role in mediating oncogenesis ( 32 , 33 ). In particular, interaction between Plk3 and the tumor-suppressor protein p53 were demonstrated whereby Plk3 phosphorylates Ser-20 of p53 in an ATM-dependent manner ( 33 ).…”
Section: Discussionmentioning
confidence: 99%
“…Various mechanisms have been described for PLK3 ’s potential role in mediating oncogenesis ( 32 , 33 ). In particular, interaction between Plk3 and the tumor-suppressor protein p53 were demonstrated whereby Plk3 phosphorylates Ser-20 of p53 in an ATM-dependent manner ( 33 ). Knocking out PLK3 attenuated S20 phosphorylation as well as transactivation and oncogenicity of gain-of-function mutated p53.…”
Section: Discussionmentioning
confidence: 99%