R175H and R273H are more prone to aggregation than wild-type (WT) p53, and their pathological aggregation can lead to various cancers. A recent study investigated the dynamic and structural properties of the R175H and R273H mutants in the p53 core domain (p53C) using extensive all-atom molecular dynamics simulations.

May 25, 2021 · Here, we reported that a new quinolone compound RYL-687 significantly inhibited non-small cell lung cancer (NSCLC) cells which express wild type (wt) p53, in contract to its much weaker...

Jul 13, 2012 · As published recently in Cancer Cell, p53 impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. I discuss that, while treating tumors lacking wt p53, this phenomenon can be exploited to protect normal cells from chemotherapy because all normal cells have wt p53.

May 9, 2024 · Here, we review the complexity of different layers of p53 regulation, and the recent advance of the p53 pathway in metabolism, ferroptosis, immunity, and others that contribute to tumor suppression.

The high prevalence and expression of p53 mutations in GBM makes them an important target for precision medicine therapies. Reactivating or restoring wt-p53 would be a promising therapy for many cancers. Various strategies have been explored to induce/reactivate wt-p53 or inhibit GOF mut-p53 in a wide range of cancer types, including GBM .

Mar 28, 2024 · Bottom: wild-type (WT) p53 helps maintain metabolic homeostasis and genome integrity and restrains cancer-associated processes, thereby suppressing tumorigenesis.

Aug 8, 2018 · Single residue changes, caused by hot-spot mutations of the TP53 gene in human cancer, transform wild-type (wt) p53 tumor suppressor proteins into potent oncoproteins - with gain-of-function, tumor-promoting activity.

6 days ago · Mutp53 inhibits the transactivation function of WT p53 by exerting a dominant-negative effect. Therefore, we hypothesize that WP1130 treatment may cause ubiquitinated mutp53 to undergo nuclear aggregation and proteasomal degradation, while the mutp53 that forms an adduct with WP1130 adopts a WT-like conformation. This shift toward the folded ...

In contrast, knockdown of p53 using two independent siRNAs significantly reduced the expression of circASCC3 and ASCC3 in cancer cells when treated with Cisplatin or Nutlin-3 (Fig. 2 E–G and SI Appendix, Fig. S2 B–D). We also tested whether WT p53 was required for this regulation by employing cancer cells without p53 or expressing a mutant p53.

Mar 10, 2025 · To test this hypothesis, we knocked down mutp53 in Huh7 (p53 Y220C), SNU449 (p53 A161T), and HepG2 (p53 wt) HCC cells (Fig. 1b and Supplementary Fig. S1b–d), or overexpressed p53 R175H-3XFLAG in ...