| RRC ID |
56184
|
| 著者 |
King SD, Gray CF, Song L, Nechushtai R, Gumienny TL, Mittler R, Padilla PA.
|
| タイトル |
The cisd gene family regulates physiological germline apoptosis through ced-13 and the canonical cell death pathway in Caenorhabditis elegans.
|
| ジャーナル |
Cell Death Differ
|
| Abstract |
Programmed cell death, which occurs through a conserved core molecular pathway, is important for fundamental developmental and homeostatic processes. The human iron-sulfur binding protein NAF-1/CISD2 binds to Bcl-2 and its disruption in cells leads to an increase in apoptosis. Other members of the CDGSH iron sulfur domain (CISD) family include mitoNEET/CISD1 and Miner2/CISD3. In humans, mutations in CISD2 result in Wolfram syndrome 2, a disease in which the patients display juvenile diabetes, neuropsychiatric disorders and defective platelet aggregation. The C. elegans genome contains three previously uncharacterized cisd genes that code for CISD-1, which has homology to mitoNEET/CISD1 and NAF-1/CISD2, and CISD-3.1 and CISD-3.2, both of which have homology to Miner2/CISD3. Disrupting the function of the cisd genes resulted in various germline abnormalities including distal tip cell migration defects and a significant increase in the number of cell corpses within the adult germline. This increased germ cell death is blocked by a gain-of-function mutation of the Bcl-2 homolog CED-9 and requires functional caspase CED-3 and the APAF-1 homolog CED-4. Furthermore, the increased germ cell death is facilitated by the pro-apoptotic, CED-9-binding protein CED-13, but not the related EGL-1 protein. This work is significant because it places the CISD family members as regulators of physiological germline programmed cell death acting through CED-13 and the core apoptotic machinery.
|
| 巻・号 |
26(1)
|
| ページ |
162-178
|
| 公開日 |
2019-1-1
|
| DOI |
10.1038/s41418-018-0108-5
|
| PII |
10.1038/s41418-018-0108-5
|
| PMID |
29666474
|
| PMC |
PMC6294797
|
| MeSH |
Animals
Apoptosis / genetics*
Apoptosis / physiology
Caenorhabditis elegans / genetics*
Caenorhabditis elegans Proteins / metabolism*
Calcium-Binding Proteins / metabolism
Caspases / metabolism
Germ Cells / metabolism*
Multigene Family
Proto-Oncogene Proteins c-bcl-2 / metabolism
|
| IF |
8.086
|
| 引用数 |
3
|
| リソース情報 |
| 線虫 |
tm4993 |
