Reply to Mishima et al.: MALT1 modulates GPX4 expression by regulating its stability DOI Creative Commons
Jun Wang, Long Liao, Bo Yang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(20)

Published: May 9, 2025

Language: Английский

MALT1 inhibitor MI-2 induces ferroptosis by direct targeting of GPX4 DOI Creative Commons
Eikan Mishima, Thomas J. O’Neill, Kai P. Hoefig

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(20)

Published: May 9, 2025

Language: Английский

Citations

1
p53 inhibits OTUD5 transcription to promote GPX4 degradation and induce ferroptosis in gastric cancer DOI Creative Commons
Junjing Zhang, Tongguan Tian, Xinxing Li

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Abstract Background Gastric cancer is one of the most prevalent malignant tumors within digestive system, and ferroptosis playing a crucial role in its progression. Glutathione peroxidase 4 (GPX4), key negative regulator ferroptosis, highly expressed gastric contributes to tumor growth. Targeting regulation GPX4 has emerged as promising approach induce develop effective therapy for cancer. Methods To confirm that OTUD5 deubiquitinase regulates we performed Western blotting, Co‐IP, immunofluorescence, quantitative real‐time PCR, Ub assay flow cytometry experiments. explore physiological function OUTD5, knocked out Otud5 gene mouse cell line (MFC) using CRISPR‐Cas9 eatablished subcutaneous tumour model. Immunohistochemistry (IHC) analysis was used inveatigate pathological correlation human Results We report ovarian domain‐containing 5 (OTUD5) interacts with, deubiquitylates stabilizes GPX4. depletion destabilizes GPX4, promotes lipid peroxidation sensitizes cells ferroptosis. Moreover, p53 activator nutlin‐3a suppresses transcription, leading degradation cells. Notably, only wild‐type capacity inhibit while mutations or deficiencies correlate with increased expression, promoting Additionally, silencing nutlin‐3a‐induced enhances sensitivity vivo. Subsequently, p53/OTUD5/GPX4 axis confirmed clinical samples. Conclusion Collectively, these findings elucidate mechanism whereby inactivation upregulates transcription deubiquitylate stablize resulting inhibition This discovery highlights potential therapeutic value targeting promote p53‐inactivated Key points mediates deubiquitination regulate stability. Deletion inhibits Wild type thereby inhibiting development OTUD5, expression activity are correlated correlates progression STAD.

Language: Английский

Citations

0
OTUD4 inhibits ferroptosis by stabilizing GPX4 and suppressing autophagic degradation to promote tumor progression DOI Creative Commons

Jinglian Chen,

Chengqing Huang,

Jiale Mei

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115681 - 115681

Published: May 1, 2025

Language: Английский

Citations

0
Reply to Mishima et al.: MALT1 modulates GPX4 expression by regulating its stability DOI Creative Commons
Jun Wang, Long Liao, Bo Yang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(20)

Published: May 9, 2025

Language: Английский

Citations

0