Reference - Detail
| RRC ID | 4194 |
|---|---|
| Author | Zermati Y, Mouhamad S, Stergiou L, Besse B, Galluzzi L, Boehrer S, Pauleau AL, Rosselli F, D'Amelio M, Amendola R, Castedo M, Hengartner M, Soria JC, Cecconi F, Kroemer G. |
| Title | Nonapoptotic role for Apaf-1 in the DNA damage checkpoint. |
| Journal | Mol Cell |
| Abstract |
Apaf-1 is an essential factor for cytochrome c-driven caspase activation during mitochondrial apoptosis but has also an apoptosis-unrelated function. Knockdown of Apaf-1 in human cells, knockout of apaf-1 in mice, and loss-of-function mutations in the Caenorhabditis elegans apaf-1 homolog ced-4 reveal the implication of Apaf-1/CED-4 in DNA damage-induced cell-cycle arrest. Apaf-1 loss compromised the DNA damage checkpoints elicited by ionizing irradiation or chemotherapy. Apaf-1 depletion reduced the activation of the checkpoint kinase Chk1 provoked by DNA damage, and knockdown of Chk1 abrogated the Apaf-1-mediated cell-cycle arrest. Nuclear translocation of Apaf-1, induced in vitro by exogenous DNA-damaging agents, correlated in non-small cell lung cancer (NSCLC) with the endogenous activation of Chk-1, suggesting that this pathway is clinically relevant. Hence, Apaf-1 exerts two distinct, phylogenetically conserved roles in response to mitochondrial membrane permeabilization and DNA damage. These data point to a role for Apaf-1 as a bona fide tumor suppressor. |
| Volume | 28(4) |
| Pages | 624-37 |
| Published | 2007-11-30 |
| DOI | 10.1016/j.molcel.2007.09.030 |
| PII | S1097-2765(07)00743-5 |
| PMID | 18042457 |
| MeSH | Animals Apoptosis* / drug effects Apoptotic Protease-Activating Factor 1 / deficiency Apoptotic Protease-Activating Factor 1 / metabolism* Caenorhabditis elegans / cytology Caenorhabditis elegans / drug effects Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism Calcium-Binding Proteins / metabolism Carcinoma, Non-Small-Cell Lung / enzymology Cell Cycle / drug effects Cell Line, Tumor Cell Nucleus / metabolism Checkpoint Kinase 1 Cisplatin / pharmacology Conserved Sequence DNA Damage* Embryo, Mammalian / cytology Embryo, Mammalian / drug effects Embryo, Mammalian / metabolism Humans Lung Neoplasms / enzymology Mice Phosphorylation / drug effects Phylogeny Protein Kinases / metabolism Protein Transport / drug effects |
| IF | 15.584 |
| Times Cited | 88 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Peer-review(Publons) |
| Total number of mentions | 14 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm853 |