An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways
During animal development, the proper regulation of apoptosis requires the precise spatial and temporal execution of cell-death programs, which can include both caspase-dependent and caspase-independent pathways. Although the mechanisms of caspase-dependent and -independent cell killing have been ex...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/85566 https://orcid.org/0000-0002-9964-9613 |
| _version_ | 1811089571749822464 |
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| author | Hirose, Takashi Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hirose, Takashi Horvitz, Howard Robert |
| author_sort | Hirose, Takashi |
| collection | MIT |
| description | During animal development, the proper regulation of apoptosis requires the precise spatial and temporal execution of cell-death programs, which can include both caspase-dependent and caspase-independent pathways. Although the mechanisms of caspase-dependent and -independent cell killing have been examined extensively, how these pathways are coordinated within a single cell that is fated to die is unknown. Here we show that the Caenorhabditis elegans Sp1 transcription factor SPTF-3 specifies the programmed cell deaths of at least two cells—the sisters of the pharyngeal M4 motor neuron and the AQR sensory neuron—by transcriptionally activating both caspase-dependent and -independent apoptotic pathways. SPTF-3 directly drives the transcription of the gene egl-1, which encodes a BH3-only protein that promotes apoptosis through the activation of the CED-3 caspase. In addition, SPTF-3 directly drives the transcription of the AMP-activated protein kinase-related gene pig-1, which encodes a protein kinase and functions in apoptosis of the M4 sister and AQR sister independently of the pathway that activates CED-3. Thus, a single transcription factor controls two distinct cell-killing programs that act in parallel to drive apoptosis. Our findings reveal a bivalent regulatory node for caspase-dependent and -independent pathways in the regulation of cell-type-specific apoptosis. We propose that such nodes might act as features of a general mechanism for regulating cell-type-specific apoptosis and could be therapeutic targets for diseases involving the dysregulation of apoptosis through multiple cell-killing mechanisms. |
| first_indexed | 2024-09-23T14:21:19Z |
| format | Article |
| id | mit-1721.1/85566 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:21:19Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
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| spelling | mit-1721.1/855662022-10-01T20:47:05Z An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways Hirose, Takashi Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology Hirose, Takashi Horvitz, H. Robert During animal development, the proper regulation of apoptosis requires the precise spatial and temporal execution of cell-death programs, which can include both caspase-dependent and caspase-independent pathways. Although the mechanisms of caspase-dependent and -independent cell killing have been examined extensively, how these pathways are coordinated within a single cell that is fated to die is unknown. Here we show that the Caenorhabditis elegans Sp1 transcription factor SPTF-3 specifies the programmed cell deaths of at least two cells—the sisters of the pharyngeal M4 motor neuron and the AQR sensory neuron—by transcriptionally activating both caspase-dependent and -independent apoptotic pathways. SPTF-3 directly drives the transcription of the gene egl-1, which encodes a BH3-only protein that promotes apoptosis through the activation of the CED-3 caspase. In addition, SPTF-3 directly drives the transcription of the AMP-activated protein kinase-related gene pig-1, which encodes a protein kinase and functions in apoptosis of the M4 sister and AQR sister independently of the pathway that activates CED-3. Thus, a single transcription factor controls two distinct cell-killing programs that act in parallel to drive apoptosis. Our findings reveal a bivalent regulatory node for caspase-dependent and -independent pathways in the regulation of cell-type-specific apoptosis. We propose that such nodes might act as features of a general mechanism for regulating cell-type-specific apoptosis and could be therapeutic targets for diseases involving the dysregulation of apoptosis through multiple cell-killing mechanisms. Howard Hughes Medical Institute 2014-03-10T14:57:26Z 2014-03-10T14:57:26Z 2013-07 2012-09 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/85566 Hirose, Takashi, and H. Robert Horvitz. “An Sp1 Transcription Factor Coordinates Caspase-Dependent and -Independent Apoptotic Pathways.” Nature 500, no. 7462 (July 14, 2013): 354–358. https://orcid.org/0000-0002-9964-9613 en_US http://dx.doi.org/10.1038/nature12329 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Hirose, Takashi Horvitz, Howard Robert An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways |
| title | An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways |
| title_full | An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways |
| title_fullStr | An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways |
| title_full_unstemmed | An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways |
| title_short | An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways |
| title_sort | sp1 transcription factor coordinates caspase dependent and independent apoptotic pathways |
| url | http://hdl.handle.net/1721.1/85566 https://orcid.org/0000-0002-9964-9613 |
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