ArticleCell death and differentiation2015
Caspase-2 impacts lung tumorigenesis and chemotherapy response in vivo.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Reciprocal compensation of caspase-2 and p53 regulates the DNA damage response in HCT116 colon cancer cells.The Journal of biological chemistry · 2026Article
- PARP4 ADP-ribosylates PIDD1 to complete a phospho/SUMO/PAR-ylation cascade that orchestrates PIDDosome assembly.Science advances · 2026Article
- Ally or traitor: the dual role of p62 in caspase-2 regulation.Cell death & disease · 2024Article
- Stepwise phosphorylation and SUMOylation of PIDD1 drive PIDDosome assembly in response to DNA repair failure.Nature communications · 2024Article
- Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia.Science advances · 2024Article
- Chemoproteomics Identifies State-Dependent and Proteoform-Selective Caspase-2 Inhibitors.Journal of the American Chemical Society · 2024Article
- Caspase-2 protects against ferroptotic cell death.Cell death & disease · 2024Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Review
- The caspase-2 substrate p54nrb exhibits a multifaceted role in tumor cell death susceptibility via gene regulatory functions.Cell death & disease · 2022Article
- Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis.Oncogene · 2022Article
- The p53-caspase-2 axis in the cell cycle and DNA damage response.Experimental & molecular medicine · 2021Review
- Phosphorylation by Aurora B kinase regulates caspase-2 activity and function.Cell death and differentiation · 2021Article
- A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest.Cell reports · 2020Article
- Targeting apoptotic caspases in cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Caspase-2 Substrates: To Apoptosis, Cell Cycle Control, and Beyond.Frontiers in cell and developmental biology · 2020Review
- Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling.Cell death & disease · 2019Article
- Dimer-specific immunoprecipitation of active caspase-2 identifies TRAF proteins as novel activators.The EMBO journal · 2018Article
- Acute Hepatopancreatic Necrosis Disease (AHPND) related microRNAs in Litopenaeus vannamei infected with AHPND-causing strain of Vibrio parahemolyticus.BMC genomics · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Caspase-2 is an atypical caspase that regulates apoptosis, cell cycle arrest and genome maintenance, although the mechanisms are not well understood. Caspase-2 has also been implicated in chemotherapy response in lung cancer, but this function has not been addressed in vivo. Here we show that Caspase-2 functions as a tumor suppressor in Kras-driven lung cancer in vivo. Loss of Caspase-2 leads to enhanced tumor proliferation and progression. Despite being more histologically advanced, Caspase-2-deficient tumors are sensitive to chemotherapy and exhibit a significant reduction in tumor volume following repeated treatment. However, Caspase-2-deficient tumors rapidly rebound from chemotherapy with enhanced proliferation, ultimately hindering long-term therapeutic benefit. In response to DNA damage, Caspase-2 cleaves and inhibits Mdm2 and thereby promotes the stability of the tumor-suppressor p53. Caspase-2 expression levels are significantly reduced in human lung tumors with wild-type p53, in agreement with the model whereby Caspase-2 functions through Mdm2/p53 regulation. Consistently, p53 target genes including p21, cyclin G1 and Msh2 are reduced in Caspase-2-deficient tumors. Finally, we show that phosphorylation of p53-induced protein with a death domain 1 leads to Caspase-2-mediated cleavage of Mdm2, directly impacting p53 levels, activity and chemotherapy response. Together, these studies elucidate a Caspase-2-p53 signaling network that impacts lung tumorigenesis and chemotherapy response in vivo.
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Registered trials
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.