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001     296086
005     20250103121049.0
024 7 _ |a 10.1073/pnas.2419625121
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024 7 _ |a 0027-8424
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024 7 _ |a 1091-6490
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037 _ _ |a DKFZ-2025-00034
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Wang, Jun
|b 0
245 _ _ |a Deciphering the role of the MALT1-RC3H1 axis in regulating GPX4 protein stability.
260 _ _ |a Washington, DC
|c 2025
|b National Acad. of Sciences
336 7 _ |a article
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336 7 _ |a Journal Article
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520 _ _ |a Ferroptosis, a unique form of iron-dependent cell death triggered by lipid peroxidation accumulation, holds great promise for cancer therapy. Despite the crucial role of GPX4 in regulating ferroptosis, our understanding of GPX4 protein regulation remains limited. Through FACS-based genome-wide CRISPR screening, we identified MALT1 as a regulator of GPX4 protein. Inhibition of MALT1 expression enhances GPX4 ubiquitination-mediated degradation by up-regulating the E3 ubiquitin ligase RC3H1. Using both rescue assays and functional genetic screening, we demonstrate that pharmacologically targeting MALT1 triggers ferroptosis in liver cancer cells. Moreover, we show that targeting MALT1 synergizes with sorafenib or regorafenib to induce ferroptosis across multiple cancer types. These findings elucidate the modulatory effects of the MALT1-RC3H1 axis on GPX4 stability, revealing a molecular mechanism that could be exploited to induce ferroptosis for cancer therapy.
536 _ _ |a 314 - Immunologie und Krebs (POF4-314)
|0 G:(DE-HGF)POF4-314
|c POF4-314
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |a GPX4
|2 Other
650 _ 7 |a MALT1
|2 Other
650 _ 7 |a ferroptosis
|2 Other
650 _ 7 |a liver cancer
|2 Other
650 _ 7 |a Phospholipid Hydroperoxide Glutathione Peroxidase
|0 EC 1.11.1.12
|2 NLM Chemicals
650 _ 7 |a Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
|0 EC 3.4.22.-
|2 NLM Chemicals
650 _ 7 |a Ubiquitin-Protein Ligases
|0 EC 2.3.2.27
|2 NLM Chemicals
650 _ 7 |a MALT1 protein, human
|0 EC 3.4.22.-
|2 NLM Chemicals
650 _ 7 |a Sorafenib
|0 9ZOQ3TZI87
|2 NLM Chemicals
650 _ 7 |a regorafenib
|0 24T2A1DOYB
|2 NLM Chemicals
650 _ 7 |a Phenylurea Compounds
|2 NLM Chemicals
650 _ 7 |a Pyridines
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Phospholipid Hydroperoxide Glutathione Peroxidase: metabolism
|2 MeSH
650 _ 2 |a Phospholipid Hydroperoxide Glutathione Peroxidase: genetics
|2 MeSH
650 _ 2 |a Ferroptosis: genetics
|2 MeSH
650 _ 2 |a Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein: metabolism
|2 MeSH
650 _ 2 |a Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein: genetics
|2 MeSH
650 _ 2 |a Protein Stability
|2 MeSH
650 _ 2 |a Ubiquitin-Protein Ligases: metabolism
|2 MeSH
650 _ 2 |a Ubiquitin-Protein Ligases: genetics
|2 MeSH
650 _ 2 |a Sorafenib: pharmacology
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Ubiquitination
|2 MeSH
650 _ 2 |a Liver Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Liver Neoplasms: genetics
|2 MeSH
650 _ 2 |a Liver Neoplasms: drug therapy
|2 MeSH
650 _ 2 |a Liver Neoplasms: pathology
|2 MeSH
650 _ 2 |a Phenylurea Compounds: pharmacology
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic
|2 MeSH
650 _ 2 |a Pyridines
|2 MeSH
700 1 _ |a Liao, Long
|b 1
700 1 _ |a Miao, Beiping
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700 1 _ |a Yang, Bo
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700 1 _ |a Li, Botai
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700 1 _ |a Ma, Xuhui
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700 1 _ |a Fitz, Annika
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700 1 _ |a Wu, Shanshan
|b 7
700 1 _ |a He, Jia
|b 8
700 1 _ |a Zhang, Qianqian
|b 9
700 1 _ |a Ji, Shuyi
|b 10
700 1 _ |a Jin, Guangzhi
|b 11
700 1 _ |a Zhang, Jianming
|b 12
700 1 _ |a Cao, Ying
|b 13
700 1 _ |a Wang, Hui
|b 14
700 1 _ |a Qin, Wenxin
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700 1 _ |a Sun, Chong
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700 1 _ |a Bernards, René
|0 0000-0001-8677-3423
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700 1 _ |a Wang, Cun
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773 _ _ |a 10.1073/pnas.2419625121
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