ArticleCell death and differentiation2011
GRAMD4 mimics p53 and mediates the apoptotic function of p73 at mitochondria.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- HNRNPD Induces Radioresistance in Nasopharyngeal Carcinoma by Sequestering GRAMD4 mRNA in Stress Granules.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploring the Research Progress of Vascular Dementia and Key Regulatory Molecules: E2F1.International journal of molecular sciences · 2026Review
- Persistent antigen is essential for sustainingScience advances · 2026Article
- When cells rebel: a comparative genomics investigation into marsupial cancer susceptibility.Molecular biology and evolution · 2026Article
- c-Abl controls early embryonic morphogenesis through YAP/p73-dependent regulation of trophectoderm and inner cell mass lineages.Cell communication and signaling : CCS · 2026Article
- Comprehensive and Combined Omics Analysis Reveals Immune-Infiltration-Associated Alternative Splicing and RBP Regulators Contributing to Ischemia-Reperfusion Injury in Liver Transplantation.International journal of genomics · 2026Article
- Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.Cellular & molecular biology letters · 2025Review
- Aging impairs CD8 T cell responses in adoptive T-cell therapy against solid tumors.Frontiers in immunology · 2025Article
- Examining genotype-phenotype associations of GRAM domain proteins using GWAS, PheWAS and literature review in cattle, human, pig, mouse and chicken.Scientific reports · 2024Article
- Quantitative trait loci mapping provides insights into the genetic regulation of dendritic cell numbers in mouse tissues.Cell reports · 2024Article
- Hepatic Transcriptome and Its Regulation Following Soluble Epoxide Hydrolase Inhibition in Alcohol-Associated Liver Disease.The American journal of pathology · 2024Article
- ER stress activates TAp73α to promote colon cancer cell apoptosis via the PERK-ATF4 pathway.Journal of Cancer · 2023Article
- Transmembrane Membrane Readers form a Novel Class of Proteins That Include Peripheral Phosphoinositide Recognition Domains and Viral Spikes.Membranes · 2022Review
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- GRAMD4 inhibits tumour metastasis by recruiting the E3 ligase ITCH to target TAK1 for degradation in hepatocellular carcinoma.Clinical and translational medicine · 2021Article
- Omega-Class Glutathione Transferases of Carcinogenic Liver Fluke,Antioxidants (Basel, Switzerland) · 2021Article
- Molecular Pathogenesis and Interventional Strategies for Alzheimer's Disease: Promises and Pitfalls.ACS pharmacology & translational science · 2020Review
- p53-Related Transcription Targets of TAp73 in Cancer Cells-Bona Fide or Distorted Reality?International journal of molecular sciences · 2020Review
- Article
- Cytoplasmic pro-apoptotic function of the tumor suppressor p73 is mediated through a modified mode of recognition of the anti-apoptotic regulator Bcl-XThe Journal of biological chemistry · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p73, a member of the p53 family, shares high sequence homology with p53 and shows many p53-like properties: it binds to p53-DNA target sites, transactivates p53-responsive genes and induces cell cycle arrest and apoptosis. Apart from this transcription-dependent effect, less is known about the downstream mechanism(s) by which p73 controls cell fate at the mitochondria. We have previously identified GRAMD4 (alias KIAA0767 or Death-Inducing-Protein) as a novel p53-independent pro-apoptotic target of E2F1, which localizes to mitochondria. In this study, we found that p73-induced apoptosis is mediated by GRAMD4 expression and translocation to the mitochondria. We showed that this protein physically interacts with Bcl-2, promotes Bax mitochondrial relocalization and oligomerization, and is highly efficient in inducing mitochondrial membrane permeabilization with release of cytochrome c and Smac. Overexpression of p73α and p73β isoforms, but not p53, leads to direct GRAMD4 promoter transactivation. In addition, GRAMD4 induces changes in Bcl-2 and Bax protein levels. GRAMD4 transcription is activated in response to cisplatin (cDDP) in a manner dependent on endogenous p73. Using solid tumor xenografts, ectopic expression of GRAMD4 together with cDDP resulted in enhanced cancer killing. Our findings demonstrate that p73 is able to trigger apoptosis via the mitochondrial pathway by a new mechanism using pro-apoptotic GRAMD4 as mediator, and strongly support its p53-like function.
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