Feb 11, 2025 · Inhibition of LZK suppressed tumor growth in MAP3K13 -amplified xenografts derived from HNSCC patients. LZK stabilized the transcription factor c-MYC through its kinase activity and gain-of-function mutants of p53 in a kinase-independent manner.

Oct 5, 2020 · Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the...

Nov 29, 2023 · TP53 regulates MYC, and MDM2/XPO1 inhibition disrupted the c-MYC–regulated transcriptome, resulting in the synergistic induction of apoptosis in acute myeloid leukemia (AML). Unexpectedly, venetoclax-resistant AMLs express high levels of c-MYC and are vulnerable to MDM2/XPO1 inhibition in vivo.

Feb 11, 2025 · Our lead LZK-targeting PROTAC abolished the kinase-dependent (c-MYC stabilization) and kinase-independent (GOF-p53 stabilization) oncogenic signaling mechanisms downstream of LZK. Our results demonstrate the promise of targeting LZK as a potential new treatment strategy for patients with HNSCC.

Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma (HCC) that is highly related to hepatitis B infection and aflatoxin B1.

Feb 28, 2014 · In this study, we show that c-Myc is essential for the induction of apoptosis within the intestinal crypt due to the inability of c-Myc-deficient cells to efficiently upregulate p53.

It has been shown that c-Myc negatively regulates the promoter of BRD7, a transcriptional cofactor of p53 . p53 downregulates M2 macrophage polarization through the p53/MDM2/c-Myc axis . p21 may be one of the targets of p53 regulation of M2-type macrophages. p21, as a downstream of p53, is upregulated during M2-type macrophage polarization.

Oct 30, 2024 · Here, we report that excessive MYC-topoisome (MYC/topoisomerase 1/topoisomerase 2) activity acutely damages DNA-activating pATM and p53. In turn, MYC is shut off and degraded, releasing TOP1 and TOP2A from MYC topoisomes in vitro and in vivo.

We have recently identified the MYC proto-oncogene, bHLH transcription factor (MYC, best known as c-Myc)-responsive pan-cancer lncRNA c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP) as an oncogenic driver.

Oct 5, 2020 · MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown …