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| Format: | Artículo científico |
| Language: | en |
| Published: |
Nature cell biology
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40033101/ |
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| author | Fan, Yizeng Wang, Yuzhao Dan, Weichao Zhang, Yilei Nie, Li Ma, Zhiqiang Zhuang, Yanxin Liu, Bo Li, Mengxing Liu, Tianjie Wang, Zixi Ye, Leihong Wei, Yi Lei, Yuzeshi Guo, Chendong An, Jiale Wang, Chi Zhang, Yulin Zeng, Jin Wei, Wenyi Gan, Boyi Li, Lei |
| author_facet | Fan, Yizeng Wang, Yuzhao Dan, Weichao Zhang, Yilei Nie, Li Ma, Zhiqiang Zhuang, Yanxin Liu, Bo Li, Mengxing Liu, Tianjie Wang, Zixi Ye, Leihong Wei, Yi Lei, Yuzeshi Guo, Chendong An, Jiale Wang, Chi Zhang, Yulin Zeng, Jin Wei, Wenyi Gan, Boyi Li, Lei Fan, Yizeng Wang, Yuzhao Dan, Weichao Zhang, Yilei Nie, Li Ma, Zhiqiang Zhuang, Yanxin Liu, Bo Li, Mengxing Liu, Tianjie Wang, Zixi Ye, Leihong Wei, Yi Lei, Yuzeshi Guo, Chendong An, Jiale Wang, Chi Zhang, Yulin Zeng, Jin Wei, Wenyi Gan, Boyi Li, Lei |
| collection | PubMed - marine biology |
| contents | PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer. Fan, Yizeng Wang, Yuzhao Dan, Weichao Zhang, Yilei Nie, Li Ma, Zhiqiang Zhuang, Yanxin Liu, Bo Li, Mengxing Liu, Tianjie Wang, Zixi Ye, Leihong Wei, Yi Lei, Yuzeshi Guo, Chendong An, Jiale Wang, Chi Zhang, Yulin Zeng, Jin Wei, Wenyi Gan, Boyi Li, Lei Ferroptosis Protein-Arginine N-Methyltransferases Humans Animals Phospholipid Hydroperoxide Glutathione Peroxidase Methylation Arginine Mice Neoplasms F-Box-WD Repeat-Containing Protein 7 Cell Line, Tumor Female Ubiquitination Mice, Nude Mice, Inbred BALB C HEK293 Cells The activation of ferroptosis has shown great potential for cancer therapy from an unconventional perspective, but revealing the mechanisms underlying the suppression of tumour-intrinsic ferroptosis to promote tumorigenesis remains a challenging task. Here we report that methionine is metabolized into S-adenosylmethionine, which functions as a methyl-group donor to trigger symmetric dimethylation of glutathione peroxidase 4 (GPX4) at the conserved arginine 152 (R152) residue, along with a prolonged GPX4 half-life. Inhibition of protein arginine methyltransferase 5 (PRMT5), which catalyses GPX4 methylation, decreases GPX4 protein levels by impeding GPX4 methylation and increasing ferroptosis inducer sensitivity in vitro and in vivo. This methylation prevents Cullin1-FBW7 E3 ligase binding to GPX4, thereby abrogating the ubiquitination-mediated GPX4 degradation. Notably, combining PRMT5 inhibitor treatment with ferroptotic therapies markedly suppresses tumour progression in mouse tumour models. In addition, the levels of GPX4 are negatively correlated with the levels of FBW7 and a poor prognosis in patients with human carcinoma. In summary, we found that PRMT5 functions as a target for improving cancer therapy efficacy, by acting to reduce the counteraction of ferroptosis by tumour cells by means of PRMT5-enhanced GPX4 stability. |
| format | Artículo científico |
| id | pubmed_40033101 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Nature cell biology |
| record_format | pubmed |
| spellingShingle | PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer. Fan, Yizeng Wang, Yuzhao Dan, Weichao Zhang, Yilei Nie, Li Ma, Zhiqiang Zhuang, Yanxin Liu, Bo Li, Mengxing Liu, Tianjie Wang, Zixi Ye, Leihong Wei, Yi Lei, Yuzeshi Guo, Chendong An, Jiale Wang, Chi Zhang, Yulin Zeng, Jin Wei, Wenyi Gan, Boyi Li, Lei Ferroptosis Protein-Arginine N-Methyltransferases Humans Animals Phospholipid Hydroperoxide Glutathione Peroxidase Methylation Arginine Mice Neoplasms F-Box-WD Repeat-Containing Protein 7 Cell Line, Tumor Female Ubiquitination Mice, Nude Mice, Inbred BALB C HEK293 Cells PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer. Fan, Yizeng Wang, Yuzhao Dan, Weichao Zhang, Yilei Nie, Li Ma, Zhiqiang Zhuang, Yanxin Liu, Bo Li, Mengxing Liu, Tianjie Wang, Zixi Ye, Leihong Wei, Yi Lei, Yuzeshi Guo, Chendong An, Jiale Wang, Chi Zhang, Yulin Zeng, Jin Wei, Wenyi Gan, Boyi Li, Lei Ferroptosis Protein-Arginine N-Methyltransferases Humans Animals Phospholipid Hydroperoxide Glutathione Peroxidase Methylation Arginine Mice Neoplasms F-Box-WD Repeat-Containing Protein 7 Cell Line, Tumor Female Ubiquitination Mice, Nude Mice, Inbred BALB C HEK293 Cells The activation of ferroptosis has shown great potential for cancer therapy from an unconventional perspective, but revealing the mechanisms underlying the suppression of tumour-intrinsic ferroptosis to promote tumorigenesis remains a challenging task. Here we report that methionine is metabolized into S-adenosylmethionine, which functions as a methyl-group donor to trigger symmetric dimethylation of glutathione peroxidase 4 (GPX4) at the conserved arginine 152 (R152) residue, along with a prolonged GPX4 half-life. Inhibition of protein arginine methyltransferase 5 (PRMT5), which catalyses GPX4 methylation, decreases GPX4 protein levels by impeding GPX4 methylation and increasing ferroptosis inducer sensitivity in vitro and in vivo. This methylation prevents Cullin1-FBW7 E3 ligase binding to GPX4, thereby abrogating the ubiquitination-mediated GPX4 degradation. Notably, combining PRMT5 inhibitor treatment with ferroptotic therapies markedly suppresses tumour progression in mouse tumour models. In addition, the levels of GPX4 are negatively correlated with the levels of FBW7 and a poor prognosis in patients with human carcinoma. In summary, we found that PRMT5 functions as a target for improving cancer therapy efficacy, by acting to reduce the counteraction of ferroptosis by tumour cells by means of PRMT5-enhanced GPX4 stability. |
| title | PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer. |
| topic | Ferroptosis Protein-Arginine N-Methyltransferases Humans Animals Phospholipid Hydroperoxide Glutathione Peroxidase Methylation Arginine Mice Neoplasms F-Box-WD Repeat-Containing Protein 7 Cell Line, Tumor Female Ubiquitination Mice, Nude Mice, Inbred BALB C HEK293 Cells |
| url | https://pubmed.ncbi.nlm.nih.gov/40033101/ |