2020
DOI: 10.1016/j.cellsig.2020.109552
|View full text |Cite
|
Sign up to set email alerts
|

Synergistic activation of p53 by actinomycin D and nutlin-3a is associated with the upregulation of crucial regulators and effectors of innate immunity

Abstract: A B S T R A C TActinomycin D and nutlin-3a (A + N) activate p53, partly through induction of phosphorylation on Ser392. The death of A549 cells induced by A + N morphologically resembles inflammation-inducing pyroptosis -cell destruction triggered by activated caspase-1. The treatment with A + N (or camptothecin) strongly upregulated caspase-1 and its two activators: IFI16 and NLRP1, however, caspase-1 activation was not detected. A549 cells may have been primed for pyroptosis, with the absence of a crucial tr… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

4
47
0

Year Published

2020
2020
2024
2024

Publication Types

Select...
9

Relationship

0
9

Authors

Journals

citations
Cited by 27 publications
(51 citation statements)
references
References 57 publications
4
47
0
Order By: Relevance
“…In addition, Ser392 phosphorylation drives p53 mitochondrial translocation and transcription-independent apoptosis in lung cancers (42). Low dose Nutlin-3a combined with actinomycin D synergistically activate p53, but cannot induce apoptosis (43). In our study, we have found high dose Nutlin-3 is able to trigger p53-dependent apoptosis and to induce IFI16 expression.…”
Section: Discussionmentioning
confidence: 46%
“…In addition, Ser392 phosphorylation drives p53 mitochondrial translocation and transcription-independent apoptosis in lung cancers (42). Low dose Nutlin-3a combined with actinomycin D synergistically activate p53, but cannot induce apoptosis (43). In our study, we have found high dose Nutlin-3 is able to trigger p53-dependent apoptosis and to induce IFI16 expression.…”
Section: Discussionmentioning
confidence: 46%
“…Gene expression signatures analysis highlighted additional pathway alterations induced by Nut-3a or WIP1i single agent and combined treatments. In particular, MDM2 inhibition led to enrichment of inflammatory signatures response- and NFKB-related genes in TP53 -mut cells that was observed upon combined treatment in the TP53 -wt cells [ 57 ]. These changes may alter the crosstalk between leukemic cells and the microenvironment and provide the rationale for novel drug combinations acting on the malignant cells and the immune response.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to apoptosis, STING agonists promote pyroptosis, necrosis, and autophagy in tumor cells. [75][76][77][78][79][80] Reportedly, stimulation of p53 primes cells for the production of interferons (through STING upregulation) and may activate negative-feedback within this signaling system by enhancing the production of suppressor of cytokine signaling 1 (SOCS1).…”
Section: Dovepressmentioning
confidence: 99%