ArticleThe EMBO journal2019
Regulation of death receptor signaling by the autophagy protein TP53INP2.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Inhibition of METTL14 Alleviates OGD/R-Induced Neuronal Differentiation Injury in Neural Stem Cells Through Suppressing the Tp53inp2/Ptgs2 Axis: Potential Benefits for the Mouse MCAO Model.CNS neuroscience & therapeutics · 2026Article
- A C-terminal cytoplasmic retention motif and nuclear localization signal regulates nuclear import of TP53INP2.Journal of cell science · 2025Article
- Review
- TP53INP2-dependent activation of muscle autophagy ameliorates sarcopenia and promotes healthy aging.Autophagy · 2024Article
- Cytoplasmic TP53INP2 acts as an apoptosis partner in TRAIL treatment: the synergistic effect of TRAIL with venetoclax in TP53INP2-positive acute myeloid leukemia.Journal of experimental & clinical cancer research : CR · 2024Article
- A genomic perspective of the aging human and mouse lung with a focus on immune response and cellular senescence.Immunity & ageing : I & A · 2023Article
- MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.Cell death & disease · 2023Article
- Inactivation of ZSCAN18 by promoter hypermethylation drives the proliferation via attenuating TP53INP2-mediated autophagy in gastric cancer cells.Clinical epigenetics · 2023Article
- Cytoplasmic Expression of TP53INP2 Modulated by Demethylase FTO and Mutant NPM1 Promotes Autophagy in Leukemia Cells.International journal of molecular sciences · 2023Article
- Natural compounds targeting mitochondrial dysfunction: emerging therapeutics for target organ damage in hypertension.Frontiers in pharmacology · 2023Review
- Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy.International journal of molecular sciences · 2022Article
- Article
- Evolutionary Diversity and Function of Metacaspases in Plants: Similar to but Not Caspases.International journal of molecular sciences · 2022Review
- Overexpression of TP53INP2 Promotes Apoptosis in Clear Cell Renal Cell Cancer via Caspase-8/TRAF6 Signaling Pathway.Journal of immunology research · 2022Article
- Identification of Two Novel CIL-102 Upregulations of ERP29 and FUMH to Inhibit the Migration and Invasiveness of Colorectal Cancer Cells by Using the Proteomic Approach.Biomolecules · 2021Article
- Impact of FasL Stimulation on Sclerostin Expression and Osteogenic Profile in IDG-SW3 Osteocytes.Biology · 2021Article
- Ursolic acid derivative UA232 evokes apoptosis of lung cancer cells induced by endoplasmic reticulum stress.Pharmaceutical biology · 2020Article
- Long non-coding RNA regulation of TRAIL in breast cancer: A tangle of non-coding threads.Oncology letters · 2020Review
- Article
- Tumor protein p53-induced nuclear protein 2 modulates osteogenic differentiation of human adipose derived stem/stromal cells by activating Wnt/β-catenin signaling.American journal of translational research · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TP53INP2 positively regulates autophagy by binding to Atg8 proteins. Here, we uncover a novel role of TP53INP2 in death-receptor signaling. TP53INP2 sensitizes cells to apoptosis induced by death receptor ligands. In keeping with this, TP53INP2 deficiency in cultured cells or mouse livers protects against death receptor-induced apoptosis. TP53INP2 binds caspase-8 and the ubiquitin ligase TRAF6, thereby promoting the ubiquitination and activation of caspase-8 by TRAF6. We have defined a TRAF6-interacting motif (TIM) and a ubiquitin-interacting motif in TP53INP2, enabling it to function as a scaffold bridging already ubiquitinated caspase-8 to TRAF6 for further polyubiquitination of caspase-8. Mutations of key TIM residues in TP53INP2 abrogate its interaction with TRAF6 and caspase-8, and subsequently reduce levels of death receptor-induced apoptosis. A screen of cancer cell lines showed that those with higher protein levels of TP53INP2 are more prone to TRAIL-induced apoptosis, making TP53INP2 a potential predictive marker of cancer cell responsiveness to TRAIL treatment. These findings uncover a novel mechanism for the regulation of caspase-8 ubiquitination and reveal TP53INP2 as an important regulator of the death receptor pathway.
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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.