Evidence map›Paper›PMID 25751141›Full record

ArticleNature cell biology2015

Ppm1b negatively regulates necroptosis through dephosphorylating Rip3.

Wanze Chen, Jianfeng Wu, Lisheng Li, Zhengmao Zhang, Junming Ren, Yaoji Liang, Fenfang Chen, Chao Yang, Zhenru Zhou, Sheng Sean Su and 8 more

Abstract read
In one paragraph

Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
8.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 157 citations in OpenAlex.

  1. Review
  2. Article
  3. Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026
    Review
  4. Article
  5. PPM1B utilizes a trinuclear metal architecture for phosphatase activity.bioRxiv : the preprint server for biology · 2026
    Article
  6. Review
  7. Selective peroxynitrite-mediated protein nitration catalyzed by glyoxalase domain containing protein 4.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 2 countries.

Wanze ChenState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Jianfeng WuState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Lisheng LiState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Zhengmao Zhang1] Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China [2] Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Junming RenState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Yaoji LiangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Fenfang ChenLife Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Chao YangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Zhenru ZhouState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Sheng Sean SuState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Xinru ZhengState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Zhirong ZhangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Chuan-Qi ZhongState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Haoqiang WanState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Mu XiaoLife Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Xia LinDepartment of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Xin-Hua Feng1] Life Sciences Institute, and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China [2] Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Jiahuai HanState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
Xiamen University · CNZhejiang University · CNBaylor College of Medicine · US

Funding

Regulation of TGF-beta Receptor Signaling by HSP90R01GM063773 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI FENG, XIN-HUA · 2001 to 2010
$2.3M
Tumor Suppressor Function of Smad4 by UbiquitinR01CA108454 · NCI · BAYLOR COLLEGE OF MEDICINE · PI FENG, XIN-HUA · 2004 to 2010
$1.8M
Roles of Smad1 Dephosphorylation in Osteoblast DifferentiationR01AR053591 · NIAMS · BAYLOR COLLEGE OF MEDICINE · PI FENG, XIN-HUA · 2008 to 2012
$1.5M
NCI NIH HHS R01 CA108454NCI NIH HHS R01CA108454NIAMS NIH HHS R01 AR053591NIAMS NIH HHS R01AR053591NIGMS NIH HHS R01 GM063773NIGMS NIH HHS R01GM63773
6 · The paper itself

Abstract

The auto-phosphorylation of murine receptor-interacting protein 3 (Rip3) on Thr 231 and Ser 232 in the necrosome is required to trigger necroptosis. However, how Rip3 phosphorylation is regulated is still largely unknown. Here we identified protein phosphatase 1B (Ppm1b) as a Rip3 phosphatase and found that Ppm1b restricts necroptosis in two settings: spontaneous necroptosis caused by Rip3 auto-phosphorylation in resting cells, and tumour necrosis factor-α (TNF)-induced necroptosis in cultured cells. We revealed that Ppm1b selectively suppresses necroptosis through the dephosphorylation of Rip3, which then prevents the recruitment of mixed lineage kinase domain-like protein (Mlkl) to the necrosome. We further showed that Ppm1b deficiency (Ppm1b(d/d)) in mice enhanced TNF-induced death in a Rip3-dependent manner, and the role of Ppm1b in inhibiting necroptosis was evidenced by elevated Rip3 phosphorylation and tissue damage in the caecum of TNF-treated Ppm1b(d/d) mice. These data indicate that Ppm1b negatively regulates necroptosis through dephosphorylating Rip3 in vitro and in vivo.

Indexed as

3T3 CellsAnimalsApoptosisCecumCell LineGene Knockout TechniquesHeLa CellsHumansMiceMice, Inbred C57BLMice, KnockoutPhosphoprotein PhosphatasesPhosphorylationProtein KinasesProtein Phosphatase 2CReceptor-Interacting Protein Serine-Threonine KinasesMLKL protein, mousePhosphoprotein PhosphatasesPPM1B protein, humanPpm1b protein, mouseProtein KinasesProtein Phosphatase 2CReceptor-Interacting Protein Serine-Threonine KinasesRipk3 protein, mouseRNA, Small InterferingTumor Necrosis Factor-alpha

Identifiers

PMID25751141
PMCPMC4523090
OpenAlexW2049463960

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.