論文 - 詳細
| RRC ID | 46611 |
|---|---|
| 著者 | Hirose T, Galvin BD, Horvitz HR. |
| タイトル | Six and Eya promote apoptosis through direct transcriptional activation of the proapoptotic BH3-only gene egl-1 in Caenorhabditis elegans. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
The decision of a cell to undergo programmed cell death is tightly regulated during animal development and tissue homeostasis. Here, we show that the Caenorhabditis elegans Six family homeodomain protein C. elegans homeobox (CEH-34) and the Eyes absent ortholog EYA-1 promote the programmed cell death of a specific pharyngeal neuron, the sister of the M4 motor neuron. Loss of either ceh-34 or eya-1 function causes survival of the M4 sister cell, which normally undergoes programmed cell death. CEH-34 physically interacts with the conserved EYA domain of EYA-1 in vitro. We identify an egl-1 5' cis-regulatory element that controls the programmed cell death of the M4 sister cell and show that CEH-34 binds directly to this site. Expression of the proapoptotic gene egl-1 in the M4 sister cell requires ceh-34 and eya-1 function. We conclude that an evolutionarily conserved complex that includes CEH-34 and EYA-1 directly activates egl-1 expression through a 5' cis-regulatory element to promote the programmed cell death of the M4 sister cell. We suggest that the regulation of apoptosis by Six and Eya family members is conserved in mammals and involved in human diseases caused by mutations in Six and Eya. |
| 巻・号 | 107(35) |
| ページ | 15479-84 |
| 公開日 | 2010-8-31 |
| DOI | 10.1073/pnas.1010023107 |
| PII | 1010023107 |
| PMID | 20713707 |
| PMC | PMC2932601 |
| MeSH | Amino Acid Sequence Animals Animals, Genetically Modified Apoptosis* Binding Sites / genetics Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Survival Gene Expression Regulation, Developmental Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Microscopy, Fluorescence Molecular Sequence Data Mutation Nuclear Proteins / genetics Nuclear Proteins / metabolism* Pharynx / cytology Pharynx / embryology Pharynx / metabolism Protein Binding Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism* Regulatory Sequences, Nucleic Acid / genetics Repressor Proteins / genetics Repressor Proteins / metabolism* Sequence Homology, Amino Acid Transcription Factors / genetics Transcription Factors / metabolism* Transcriptional Activation |
| IF | 9.412 |
| 引用数 | 23 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY |
| リソース情報 | |
| 線虫 | tm591 |