title: Interaction with Pyruvate Kinase M2 Destabilizes Tristetraprolin by Proteasome Degradation and Regulates Cell Proliferation in Breast Cancer.
abstract: Pyruvate kinase M2 (PKM2), which is predominantly expressed in most cancers, plays a key role in the Warburg effect. However, how PKM2 functions as a tumor supportive protein has not been fully elucidated. Here, we identified tristetraprolin (TTP), an AU-rich, element-binding protein that regulates mRNA stability, as a new binding partner of PKM2. Our data reveal that PKM2 suppresses TTP protein levels by promoting its phosphorylation, ubiquitination, and proteasome degradation, reducing its mRNA turnover ability and ultimately impairing cell viability in breast cancer cells. The p38/mitogen-activated protein kinase (MAPK) pathway might be involved in PKM2-mediated TTP degradation, while treatment with the p38 inhibitor or siRNA abolished PKM2-induced TTP protein degradation. These findings demonstrate that PKM2-TTP association is crucial for regulating breast cancer cell proliferation and is therefore a potential therapeutic target in cancer.
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China.|Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Liangqian
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.|School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China.
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China.|Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China.|Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D011770:Pyruvate Kinase / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D013963:Thyroid Hormones / Q000378:metabolism*; D051816:Tristetraprolin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex; D011770:Pyruvate Kinase; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013963:Thyroid Hormones; D051816:Tristetraprolin; D048051:p38 Mitogen-Activated Protein Kinases; D000097810:Thyroid Hormone-Binding Proteins