TPI1 promotes p53 ubiquitination in bladder cancer by recruiting AKT to enhance MDM2 phosphorylation DOI Creative Commons
Chenyang Wang, Shun Wan, Kunpeng Li

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 215, P. 107695 - 107695

Published: March 15, 2025

Bladder cancer (BCa) is an aggressive malignancy with limited effective treatment options, and its poor outcomes largely result from delayed detection therapeutic resistance. Triosephosphate isomerase 1 (TPI1) has been associated tumor progression in various cancers, but specific function BCa remains poorly characterized. This study evaluated cancer-related markers identified glycolysis as a key factor negatively impacting survival BCa. Additionally, TPI1 was recognized potential prognostic marker, expression significantly elevated tissues compared to normal counterparts. Higher levels were strongly linked unfavorable clinical outcomes. Functional assays demonstrated that overexpression promoted cell growth, migration, invasive capabilities vitro vivo. Mechanistically, interacted serine/threonine kinase B (AKT) murine double minute 2 (MDM2) form protein complex, which enhanced the AKT-driven phosphorylation of MDM2 at serine 166 site, thereby promoting p53 (p53) ubiquitination degradation. Furthermore, truncated MDM2-F2 mutant (spanning 181-360) bound TPI1, amino acid 317 playing critical role this interaction. Notably, reducing AKT counteracted triggered by TPI1.

Language: Английский

TPI1 promotes p53 ubiquitination in bladder cancer by recruiting AKT to enhance MDM2 phosphorylation DOI Creative Commons
Chenyang Wang, Shun Wan, Kunpeng Li

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 215, P. 107695 - 107695

Published: March 15, 2025

Bladder cancer (BCa) is an aggressive malignancy with limited effective treatment options, and its poor outcomes largely result from delayed detection therapeutic resistance. Triosephosphate isomerase 1 (TPI1) has been associated tumor progression in various cancers, but specific function BCa remains poorly characterized. This study evaluated cancer-related markers identified glycolysis as a key factor negatively impacting survival BCa. Additionally, TPI1 was recognized potential prognostic marker, expression significantly elevated tissues compared to normal counterparts. Higher levels were strongly linked unfavorable clinical outcomes. Functional assays demonstrated that overexpression promoted cell growth, migration, invasive capabilities vitro vivo. Mechanistically, interacted serine/threonine kinase B (AKT) murine double minute 2 (MDM2) form protein complex, which enhanced the AKT-driven phosphorylation of MDM2 at serine 166 site, thereby promoting p53 (p53) ubiquitination degradation. Furthermore, truncated MDM2-F2 mutant (spanning 181-360) bound TPI1, amino acid 317 playing critical role this interaction. Notably, reducing AKT counteracted triggered by TPI1.

Language: Английский

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