Evidence map›Paper›PMID 42682528›Full record

ArticleFrontiers in oncology2026

AMPK-PP1/PP2 axis regulates GSDMD-mediated pyroptosis via phosphorylation.

Ting Zhang, Chunxiao Gao, Jixuan Xu, Weishan Zhang, Yamin Xing, Guangyuan Li, Mengxue Li, Yanwei Guo, Zisen Zhang, Pengyuan Zheng and 2 more

Abstract read
In one paragraph

Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Ting Zhang *Zhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis and Treatment in Oncology, Oncology Department, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Chunxiao Gao *Zhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis and Treatment in Oncology, Oncology Department, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Jixuan XuDepartment of Gastrointestinal and Thyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Weishan ZhangDepartment of Gastrointestinal and Thyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Yamin XingMarshall B. J. Medical Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Guangyuan LiZhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis and Treatment in Oncology, Oncology Department, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Mengxue LiMarshall B. J. Medical Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Yanwei GuoZhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis and Treatment in Oncology, Oncology Department, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zisen ZhangZhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis and Treatment in Oncology, Oncology Department, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Pengyuan ZhengMarshall B. J. Medical Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Xiaoke ZhengZhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis and Treatment in Oncology, Oncology Department, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Xiufeng ChuZhengzhou Key Laboratory of Lipid Metabolism and Precision Diagnosis and Treatment in Oncology, Oncology Department, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gasdermin D (GSDMD), the most important executor of pyroptosis, is activated through caspase cleavage to release the N-terminal fragment (GD-NT), which oligomerizes and forms pores in the plasma membrane to induce pyroptosis. We previously reported that AMP-activated protein kinase (AMPK) phosphorylates GD-NT, thereby inhibiting its cytolytic activity. Here, we further investigated the role of phosphorylation in GD-NT-mediated pyroptosis and found that the specific AMPK agonist A-769662 protected tumor cells from GD-NT-mediated pyroptosis and that metformin significantly reduced interleukin 1β (IL-1β) and IL-18 in the peritoneal fluid of lipopolysaccharide (LPS)-induced septic mice. Importantly, we identified PP1/PP2 as the key phosphatases that dephosphorylate GD-NT at Ser46. Treatment of cells with the phosphatase inhibitor okadaic acid (OA) significantly enhanced the phosphorylation of GD-NT and reduced GD-NT-mediated pyroptosis. Therefore, we conclude that the AMPK-PP1/PP2 axis is a regulatory mechanism in pyroptosis. Pharmacological targeting of AMPK-PP1/PP2 provides a potential strategy for pyroptosis-related diseases.

Indexed as

AMPKGSDMDmetforminPP1/PP2pyroptosis

Identifiers

PMID42682528
PMCPMC13529552

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