Deficiency of PPP6C protects TNF-induced necroptosis through activation of TAK1

Zou, Yanbiao; Zheng, Qi; Jiang, Bin; Liu, Yuning; Xu, Yeqiong; Ma, Liang; Hu, Zonghao; Wu, Ming; Song, Hai

doi:10.1038/s41419-022-05076-1

Cited by 11 publications

(9 citation statements)

References 71 publications

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“…Inhibition of TAK1, by the virulence factor Yersinia outer protein J (YopJ) expressed by Yersinia species bacteria or the pharmacological TAK1 inhibitor 5Z-7-Oxozeaenol (5z7), prevents the IKKα/β-mediated phosphorylation of RIPK1 at S25 and results in TNF-induced RIPK1-mediated cell death [ 123 ]. TAK1 activity is controlled by TAK1-binding protein 2 (TAB2) [ 129 ] and protein phosphatase 6 catalytic subunit (PPP6C) [ 130 ] and in their absence TAK1 is hyperactivated. However, where PPP6C deficiency prevents TNF-induced RIPK1-mediated necroptosis [ 130 ], abrogation of TAB2 leads to an exacerbation of TNF-induced necroptosis mediated by RIPK3 [ 127 ].…”

Section: Post-translational Modifications That Influence Apoptosis An...mentioning

confidence: 99%

“…TAK1 activity is controlled by TAK1-binding protein 2 (TAB2) [ 129 ] and protein phosphatase 6 catalytic subunit (PPP6C) [ 130 ] and in their absence TAK1 is hyperactivated. However, where PPP6C deficiency prevents TNF-induced RIPK1-mediated necroptosis [ 130 ], abrogation of TAB2 leads to an exacerbation of TNF-induced necroptosis mediated by RIPK3 [ 127 ]. Moreover, deletion of TAB2 sensitizes PPP6C-deficient cells to necroptosis [ 130 ].…”

Section: Post-translational Modifications That Influence Apoptosis An...mentioning

confidence: 99%

“…However, where PPP6C deficiency prevents TNF-induced RIPK1-mediated necroptosis [ 130 ], abrogation of TAB2 leads to an exacerbation of TNF-induced necroptosis mediated by RIPK3 [ 127 ]. Moreover, deletion of TAB2 sensitizes PPP6C-deficient cells to necroptosis [ 130 ]. This indicates that TAB2 restricts necroptosis in a currently unappreciated manner.…”

Section: Post-translational Modifications That Influence Apoptosis An...mentioning

confidence: 99%

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Mechanisms of TNF-independent RIPK3-mediated cell death

Tummers

Green

2022

Biochemical Journal

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Apoptosis and necroptosis regulate many aspects of organismal biology and are involved in various human diseases. TNF is well known to induce both of these forms of cell death and the underlying mechanisms have been elaborately described. However, cells can also engage apoptosis and necroptosis through TNF-independent mechanisms, involving, for example, activation of the pattern recognition receptors Toll-like receptor (TLR)-3 and -4, or zDNA-binding protein 1 (ZBP1). In this context, cell death signaling depends on the presence of receptor-interacting serine/threonine protein kinase 3 (RIPK3). Whereas RIPK3 is required for TNF-induced necroptosis, it mediates both apoptosis and necroptosis upon TLR3/4 and ZBP1 engagement. Here, we review the intricate mechanisms by which TNF-independent cell death is regulated by RIPK3.

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Section: Post-translational Modifications That Influence Apoptosis An...mentioning

confidence: 99%

Section: Post-translational Modifications That Influence Apoptosis An...mentioning

confidence: 99%

Section: Post-translational Modifications That Influence Apoptosis An...mentioning

confidence: 99%

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Mechanisms of TNF-independent RIPK3-mediated cell death

Tummers

Green

2022

Biochemical Journal

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“…Recently, Zou et al . [ 21 ] reported that deletion of Ppp6c does not significantly affect proliferation of L929 cells. We also found that Ppp6c deletion using Nestin‐Cre has little effect on cell proliferation in the brain (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

“…[21] reported 550 FEBS Open Bio 14 (2024) 545-554 ª 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.…”

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confidence: 99%

Oncogenic K‐Ras^G12V cannot overcome proliferation failure caused by loss of Ppp6c in mouse embryonic fibroblasts

Ito,

Tanuma,

Kotani

et al. 2024

FEBS Open Bio

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Protein phosphatase 6 is a Ser/Thr protein phosphatase and its catalytic subunit is Ppp6c. Ppp6c is thought to be indispensable for proper growth of normal cells. On the other hand, loss of Ppp6c accelerates growth of oncogenic Ras‐expressing cells. Although it has been studied in multiple contexts, the role(s) of Ppp6c in cell proliferation remains controversial. It is unclear how oncogenic K‐Ras overcomes cell proliferation failure induced by Ppp6c deficiency; therefore, in this study, we attempted to shed light on how oncogenic K‐Ras modulates tumor cell growth. Contrary to our expectations, loss of Ppp6c decreased proliferation, anchorage‐independent growth in soft agar, and tumor formation of oncogenic Ras‐expressing mouse embryonic fibroblasts (MEFs). These findings show that oncogenic K‐RasG12V cannot overcome proliferation failure caused by loss of Ppp6c in MEFs.

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Let’s make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment

Bayat,

Nahand

2024

Cell Biol Toxicol

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Advancements in the CRISPR technology, a game-changer in experimental research, have revolutionized various fields of life sciences and more profoundly, cancer research. Cell death pathways are among the most deregulated in cancer cells and are considered as critical aspects in cancer development. Through decades, our knowledge of the mechanisms orchestrating programmed cellular death has increased substantially, attributed to the revolution of cutting-edge technologies. The heroic appearance of CRISPR systems have expanded the available screening platform and genome engineering toolbox to detect mutations and create precise genome edits. In that context, the precise ability of this system for identification and targeting of mutations in cell death signaling pathways that result in cancer development and therapy resistance is an auspicious choice to transform and accelerate the individualized cancer therapy. The concept of personalized cancer therapy stands on the identification of molecular characterization of the individual tumor and its microenvironment in order to provide a precise treatment with the highest possible outcome and minimum toxicity. This study explored the potential of CRISPR technology in precision cancer treatment by identifying and targeting specific cell death pathways. It showed the promise of CRISPR in finding key components and mutations involved in programmed cell death, making it a potential tool for targeted cancer therapy. However, this study also highlighted the challenges and limitations that need to be addressed in future research to fully realize the potential of CRISPR in cancer treatment. Graphical abstract Current application of CRISPR system in cancer therapy through a glance. A choosing the appropriate biological model for screening in vitro (using established cell lines, animal derived tumor cells, human derived tumor cells, stem cells or T cells), in vivo (using animal models which can harbor human derived tumor), or ex vivo (human/animal-derived organoids). B preparation of CRISPR gRNA library. C experimental design of CRISPR screening, identification of the desired gRNAs or phenotypic response. D CRISPR-Cas targeting of the identified targets, with Cas9 gene editing system (Knockout, base editing, prime editing), RNA modulation (modulation of RNA splicing, RNA base editing, RNA interference), and epigenomic edits and CRISPR interference/activation using dead Cas9 (dCas9) (Bock et al. 2022b)

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Deficiency of PPP6C protects TNF-induced necroptosis through activation of TAK1

Cited by 11 publications

References 71 publications

Mechanisms of TNF-independent RIPK3-mediated cell death

Mechanisms of TNF-independent RIPK3-mediated cell death

Oncogenic K‐Ras^G12V cannot overcome proliferation failure caused by loss of Ppp6c in mouse embryonic fibroblasts

Let’s make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment

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Deficiency of PPP6C protects TNF-induced necroptosis through activation of TAK1

Cited by 11 publications

References 71 publications

Mechanisms of TNF-independent RIPK3-mediated cell death

Mechanisms of TNF-independent RIPK3-mediated cell death

Oncogenic K‐RasG12V cannot overcome proliferation failure caused by loss of Ppp6c in mouse embryonic fibroblasts

Let’s make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment

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Product

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Oncogenic K‐Ras^G12V cannot overcome proliferation failure caused by loss of Ppp6c in mouse embryonic fibroblasts