POPX2 phosphatase regulates apoptosis through the TAK1-IKK-NF-κB pathway.


:Chemoresistance is one of the leading causes that contributes to tumor relapse and poor patient outcome after several rounds of drug therapy. The causes of chemoresistance are multi-factorial. Ultimately, it is the balance of pro- and anti-apoptotic activities in the cells. We have previously reported links between POPX2 serine/threonine phosphatase with cell motility and invasiveness of breast cancer cells. Here, we show that POPX2 plays a role in the regulation of apoptosis. The effect of POPX2 on apoptosis centers on the inactivation of TGF-β activated kinase (TAK1). TAK1 is essential for several important biological functions including innate immunity, development and cell survival. We find that POPX2 interacts directly with TAK1 and is able to dephosphorylate TAK1. Cells with lower levels of POPX2 exhibit higher TAK1 activity in response to etoposide (VP-16) treatment. This subsequently leads to increased translocation of NF-κB from the cytosol to the nucleus. Consequently, NF-κB-mediated transcription of anti-apoptotic proteins is upregulated to promote cell survival. On the other hand, cells with higher levels of POPX2 are more vulnerable to apoptosis induced by etoposide. Our data demonstrate that POPX2 is a negative regulator of TAK1 signaling pathway and modulates apoptosis through the regulation of TAK1 activity. As inhibition of TAK1 has been proposed to reduce chemoresistance and increase sensitivity to chemotherapy in certain types of cancer, modulation of POPX2 levels may provide an additional avenue and consideration in fine-tuning therapeutic response.


Cell Death Dis


Cell death & disease


Weng T,Koh CG




Has Abstract


2017-09-14 00:00:00












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    authors: Persano L,Pistollato F,Rampazzo E,Della Puppa A,Abbadi S,Frasson C,Volpin F,Indraccolo S,Scienza R,Basso G

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  • Regulation and biological role of the peptide/histidine transporter SLC15A3 in Toll-like receptor-mediated inflammatory responses in macrophage.

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    authors: Song F,Yi Y,Li C,Hu Y,Wang J,Smith DE,Jiang H

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  • Histone deacetylase 1 and 2 differentially regulate apoptosis by opposing effects on extracellular signal-regulated kinase 1/2.

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  • MiR-485-3p and miR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression.

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    authors: Lou C,Xiao M,Cheng S,Lu X,Jia S,Ren Y,Li Z

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  • Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors.

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    authors: Alaimo A,Lorenzoni M,Ambrosino P,Bertossi A,Bisio A,Macchia A,Zoni E,Genovesi S,Cambuli F,Foletto V,De Felice D,Soldovieri MV,Mosca I,Gandolfi F,Brunelli M,Petris G,Cereseto A,Villarroel A,Thalmann G,Carbone FG,Kr

    更新日期:2020-12-07 00:00:00

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    authors: Labi V,Erlacher M

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    journal_title:Cell death & disease

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    authors: Ather JL,Fortner KA,Budd RC,Anathy V,Poynter ME

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  • Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression.

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  • H. pylori infection confers resistance to apoptosis via Brd4-dependent BIRC3 eRNA synthesis.

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    journal_title:Cell death & disease

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    authors: Chen Y,Sheppard D,Dong X,Hu X,Chen M,Chen R,Chakrabarti J,Zavros Y,Peek RM,Chen LF

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    authors: Li L,Liu J,Xu M,Yu H,Lv C,Cao F,Wang Z,Fu Y,Zhang M,Meng H,Zhang X,Kang L,Zhang Z,Li J,Feng J,Lian X,Yu L,Zhou J

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  • Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer.

    abstract::Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA-mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expressi...

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    authors: Guo Z,Song J,Hao J,Zhao H,Du X,Li E,Kuang Y,Yang F,Wang W,Deng J,Wang Q

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    journal_title:Cell death & disease

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    authors: Castilla C,Chinchón D,Medina R,Torrubia FJ,Japón MA,Sáez C

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    authors: Ffrench B,Gasch C,Hokamp K,Spillane C,Blackshields G,Mahgoub TM,Bates M,Kehoe L,Mooney A,Doyle R,Doyle B,O'Donnell D,Gleeson N,Hennessy BT,Stordal B,O'Riain C,Lambkin H,O'Toole S,O'Leary JJ,Gallagher MF

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Miao S,Shu D,Zhu Y,Lu M,Zhang Q,Pei Y,He AD,Ma R,Zhang B,Ming ZY

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  • MicroRNA-34a: a potential therapeutic target in human cancer.

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    journal_title:Cell death & disease

    pub_type: 杂志文章,评审


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    journal_title:Cell death & disease

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    authors: Xie N,Cai JB,Zhang L,Zhang PF,Shen YH,Yang X,Lu JC,Gao DM,Kang Q,Liu LX,Zhang C,Huang XY,Zou H,Zhang XY,Song ZJ,Sun HX,Fu BM,Ke AW,Shi GM

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    journal_title:Cell death & disease

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    authors: Chen F,Li A,Gao S,Hollern D,Williams M,Liu F,VanSickle EA,Andrechek E,Zhang C,Yang C,Luo R,Xiao H

    更新日期:2014-05-22 00:00:00

  • miR-1254 inhibits cell proliferation, migration, and invasion by down-regulating Smurf1 in gastric cancer.

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Jiang M,Shi L,Yang C,Ge Y,Lin L,Fan H,He Y,Zhang D,Miao Y,Yang L

    更新日期:2019-01-10 00:00:00

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Hong P,Liu QW,Xie Y,Zhang QH,Liao L,He QY,Li B,Xu WW

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  • Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis.

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Carlisi D,Buttitta G,Di Fiore R,Scerri C,Drago-Ferrante R,Vento R,Tesoriere G

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Bleicken S,Hofhaus G,Ugarte-Uribe B,Schröder R,García-Sáez AJ

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  • MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells.

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Cardinali B,Cappella M,Provenzano C,Garcia-Manteiga JM,Lazarevic D,Cittaro D,Martelli F,Falcone G

    更新日期:2016-02-04 00:00:00

  • Mitochondrial Lon sequesters and stabilizes p53 in the matrix to restrain apoptosis under oxidative stress via its chaperone activity.

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Sung YJ,Kao TY,Kuo CL,Fan CC,Cheng AN,Fang WC,Chou HY,Lo YK,Chen CH,Jiang SS,Chang IS,Hsu CH,Lee JC,Lee AY

    更新日期:2018-06-13 00:00:00

  • Three-dimensional structure of Bax-mediated pores in membrane bilayers.

    abstract::B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) is a member of the Bcl-2 protein family having a pivotal role in triggering cell commitment to apoptosis. Bax is latent and monomeric in the cytosol but transforms into its lethal, mitochondria-embedded oligomeric form in response to cell stress, leading to the rele...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Xu XP,Zhai D,Kim E,Swift M,Reed JC,Volkmann N,Hanein D

    更新日期:2013-06-20 00:00:00

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    abstract::Autophagy is a major self-degradative process that maintains cellular homeostasis and function in mammalian cells. Autophagic dysfunction occurs in the early pathogenesis of Alzheimer's disease (AD) and directly regulates amyloid-β (Aβ) metabolism. Although it has been proven that the cytokine IFN-γ enhances autophagy...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: He Z,Yang Y,Xing Z,Zuo Z,Wang R,Gu H,Qi F,Yao Z

    更新日期:2020-06-08 00:00:00

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    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wei YL,Yang WX

    更新日期:2019-05-24 00:00:00

  • MET/SMAD3/SNAIL circuit mediated by miR-323a-3p is involved in regulating epithelial-mesenchymal transition progression in bladder cancer.

    abstract::Bladder cancer (BCa) is the one of the most common cancers with high incidence, occurrence and low 5-year survival rate. Emerging evidence indicates that DLK1-DIO3 genomic region especially the miRNA cluster in this region is involved in several pathologic processes and various cancers, and miR-323a-3p is a member of ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Li J,Xu X,Meng S,Liang Z,Wang X,Xu M,Wang S,Li S,Zhu Y,Xie B,Lin Y,Zheng X,Liu B,Xie L

    更新日期:2017-08-24 00:00:00