Multitarget mechanism of MYC inhibition by the bacterial lon protease in disease DOI Creative Commons
Inès Ambite,

Murphy Lam Yim Wan,

Tran Thi Hien

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 25, 2025

Abstract Identifying specific inhibitors of the MYC oncogene has been challenging, due to off target effects associated with inhibition. This study investigated how recombinant Escherichia coli Lon protease (rLon), which targets in human cells, inhibits over-activation models infection and cancer. In silico predictions identified peptide domains bacterial that affinity these peptides for was by surface plasmon resonance. The N-terminal domain rLon shown interact C-terminal, leucine zipper MAX prevent MYC/MAX dimerization. Furthermore, targeted degraded c-MYC vitro cellular models, through peptidase domain. a model kidney infection, treatment prevented, c-MYC, N-MYC L-MYC over-expression, MYC-dependent gene expression, specifically renal toxicity genes pathology, suggesting recognizes corrects dysregulation this disease. findings describe multitarget mechanism inhibition rLon, combined achieved domains, targeting different epitopes functions, no evidence or detrimental on homeostatic expression.

Language: Английский

MYC the oncogene from hell: Novel opportunities for cancer therapy DOI

Adriana Papadimitropoulou,

Maria Makri,

Grigoris Zoidis

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116194 - 116194

Published: Feb. 2, 2024

Language: Английский

Citations

12
Antitumor Effect of Anti‐c‐Myc Aptamer‐Based PROTAC for Degradation of the c‐Myc Protein DOI Creative Commons
Yuchun Wang, Gang Yang, Xinyu Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(26)

Published: April 29, 2024

Abstract Targeting “undruggable” targets with intrinsically disordered structures is of great significance for the treatment disease. The transcription factor c‐Myc controls global gene expression and an attractive therapeutic target multiple types cancers. However, due to lack defined ligand binding pockets, targeted have thus far been unsuccessful. Herein, address dilemma lacking ligands, efficient high throughput aptamer screening strategy established, named polystyrene microwell plate‐based systematic evolution ligands by exponential enrichment (microwell‐SELEX), identify specific (MA9C1) against c‐Myc. multifunctional aptamer‐based Proteolysis Chimeras (PROTAC) proteolysis (ProMyc) developed using MA9C1 as ligand. ProMyc not only significantly degrades ubiquitin‐proteasome system, but also reduces Max protein, synergistically inhibiting transcriptional activity. Combination artificial cyclization anti‐PD‐L1 (PA1)‐based delivery circular PA1‐ProMyc chimeras achieve tumor regression in xenograft model, laying a solid foundation development efficacious degrader clinic. Therefore, this provides invaluable potential drug discovery anti‐tumor therapy, offering promising overcome challenge targeting intractable targets.

Language: Английский

Citations

11
Polyamine metabolism and anti-tumor immunity DOI Creative Commons
Jingyi Wu, Yan Zeng,

Yu-Yang You

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 18, 2025

Growing attention has been directed toward the critical role of polyamines in tumor microenvironment and immune regulation. Polyamines, primarily comprising putrescine, spermidine, spermine, are tightly regulated through coordinated biosynthesis, catabolism, transport, with distinct metabolic patterns between normal cancerous tissues. Emerging evidence highlights pivotal polyamine metabolism initiation, progression, metastasis. This review aims to elucidate differences catabolism tissues, as well associated alterations epigenetic modifications resistance checkpoint blockade driven by metabolism. Polyamine influences both cells modulating cell phenotypes-shifting them towards either suppression or evasion within microenvironment. Additionally, impacts immunotherapy its regulation key enzymes. also explores potential therapeutic targets summarizes roles inhibitors combination for cancer treatment, offering a novel perspective on strategies.

Language: Английский

Citations

1
Intratumour oxidative hotspots provide a niche for cancer cell dissemination DOI
Yoshifumi Ueda, Shigeki Kiyonaka, Laura M. Selfors

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Language: Английский

Citations

1
Multitarget mechanism of MYC inhibition by the bacterial lon protease in disease DOI Creative Commons
Inès Ambite,

Murphy Lam Yim Wan,

Tran Thi Hien

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 25, 2025

Abstract Identifying specific inhibitors of the MYC oncogene has been challenging, due to off target effects associated with inhibition. This study investigated how recombinant Escherichia coli Lon protease (rLon), which targets in human cells, inhibits over-activation models infection and cancer. In silico predictions identified peptide domains bacterial that affinity these peptides for was by surface plasmon resonance. The N-terminal domain rLon shown interact C-terminal, leucine zipper MAX prevent MYC/MAX dimerization. Furthermore, targeted degraded c-MYC vitro cellular models, through peptidase domain. a model kidney infection, treatment prevented, c-MYC, N-MYC L-MYC over-expression, MYC-dependent gene expression, specifically renal toxicity genes pathology, suggesting recognizes corrects dysregulation this disease. findings describe multitarget mechanism inhibition rLon, combined achieved domains, targeting different epitopes functions, no evidence or detrimental on homeostatic expression.

Language: Английский

Citations

1