Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival
Previous experiments suggest a connection between the N-alpha-acetylation of proteins and sensitivity of cells to apoptotic signals. Here, we describe a biochemical assay to detect the acetylation status of proteins and demonstrate that protein N-alpha-acetylation is regulated by the availability of...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92075 https://orcid.org/0000-0002-6702-4192 |
| _version_ | 1826217054760337408 |
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| author | Yi, Caroline H. Pan, Heling Seebacher, Jan Jang, Il-Ho Hyberts, Sven G. Heffron, Gregory J. Vander Heiden, Matthew G. Yang, Renliang Li, Fupeng Locasale, Jason W. Sharfi, Hadar Zhai, Bo Rodriguez-Mias, Ricard Luithardt, Harry Cantley, Lewis C. Daley, George Q. Asara, John M. Gygi, Steven P. Wagner, Gerhard Liu, Chuan-Fa Yuan, Junying |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yi, Caroline H. Pan, Heling Seebacher, Jan Jang, Il-Ho Hyberts, Sven G. Heffron, Gregory J. Vander Heiden, Matthew G. Yang, Renliang Li, Fupeng Locasale, Jason W. Sharfi, Hadar Zhai, Bo Rodriguez-Mias, Ricard Luithardt, Harry Cantley, Lewis C. Daley, George Q. Asara, John M. Gygi, Steven P. Wagner, Gerhard Liu, Chuan-Fa Yuan, Junying |
| author_sort | Yi, Caroline H. |
| collection | MIT |
| description | Previous experiments suggest a connection between the N-alpha-acetylation of proteins and sensitivity of cells to apoptotic signals. Here, we describe a biochemical assay to detect the acetylation status of proteins and demonstrate that protein N-alpha-acetylation is regulated by the availability of acetyl-CoA. Because the antiapoptotic protein Bcl-xL is known to influence mitochondrial metabolism, we reasoned that Bcl-xL may provide a link between protein N-alpha-acetylation and apoptosis. Indeed, Bcl-xL overexpression leads to a reduction in levels of acetyl-CoA and N-alpha-acetylated proteins in the cell. This effect is independent of Bax and Bak, the known binding partners of Bcl-xL. Increasing cellular levels of acetyl-CoA by addition of acetate or citrate restores protein N-alpha-acetylation in Bcl-xL-expressing cells and confers sensitivity to apoptotic stimuli. We propose that acetyl-CoA serves as a signaling molecule that couples apoptotic sensitivity to metabolism by regulating protein N-alpha-acetylation. |
| first_indexed | 2024-09-23T16:57:19Z |
| format | Article |
| id | mit-1721.1/92075 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:57:19Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/920752022-09-29T22:36:49Z Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival Yi, Caroline H. Pan, Heling Seebacher, Jan Jang, Il-Ho Hyberts, Sven G. Heffron, Gregory J. Vander Heiden, Matthew G. Yang, Renliang Li, Fupeng Locasale, Jason W. Sharfi, Hadar Zhai, Bo Rodriguez-Mias, Ricard Luithardt, Harry Cantley, Lewis C. Daley, George Q. Asara, John M. Gygi, Steven P. Wagner, Gerhard Liu, Chuan-Fa Yuan, Junying Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Vander Heiden, Matthew G. Previous experiments suggest a connection between the N-alpha-acetylation of proteins and sensitivity of cells to apoptotic signals. Here, we describe a biochemical assay to detect the acetylation status of proteins and demonstrate that protein N-alpha-acetylation is regulated by the availability of acetyl-CoA. Because the antiapoptotic protein Bcl-xL is known to influence mitochondrial metabolism, we reasoned that Bcl-xL may provide a link between protein N-alpha-acetylation and apoptosis. Indeed, Bcl-xL overexpression leads to a reduction in levels of acetyl-CoA and N-alpha-acetylated proteins in the cell. This effect is independent of Bax and Bak, the known binding partners of Bcl-xL. Increasing cellular levels of acetyl-CoA by addition of acetate or citrate restores protein N-alpha-acetylation in Bcl-xL-expressing cells and confers sensitivity to apoptotic stimuli. We propose that acetyl-CoA serves as a signaling molecule that couples apoptotic sensitivity to metabolism by regulating protein N-alpha-acetylation. 2014-12-08T18:38:23Z 2014-12-08T18:38:23Z 2011-08 2010-07 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/92075 Yi, Caroline H., Heling Pan, Jan Seebacher, Il-Ho Jang, Sven G. Hyberts, Gregory J. Heffron, Matthew G. Vander Heiden, et al. “Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival.” Cell 146, no. 4 (August 2011): 607–620. © 2011 Elsevier Inc. https://orcid.org/0000-0002-6702-4192 en_US http://dx.doi.org/10.1016/j.cell.2011.06.050 Cell 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 Elsevier Elsevier |
| spellingShingle | Yi, Caroline H. Pan, Heling Seebacher, Jan Jang, Il-Ho Hyberts, Sven G. Heffron, Gregory J. Vander Heiden, Matthew G. Yang, Renliang Li, Fupeng Locasale, Jason W. Sharfi, Hadar Zhai, Bo Rodriguez-Mias, Ricard Luithardt, Harry Cantley, Lewis C. Daley, George Q. Asara, John M. Gygi, Steven P. Wagner, Gerhard Liu, Chuan-Fa Yuan, Junying Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival |
| title | Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival |
| title_full | Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival |
| title_fullStr | Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival |
| title_full_unstemmed | Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival |
| title_short | Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival |
| title_sort | metabolic regulation of protein n alpha acetylation by bcl xl promotes cell survival |
| url | http://hdl.handle.net/1721.1/92075 https://orcid.org/0000-0002-6702-4192 |
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