A systematic analysis of the PARP protein family identifies new functions critical for cell physiology
The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD[superscript +] as their substrate to modify acceptor proteins with ADP-ribose modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analy...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/96281 |
| _version_ | 1826199178620960768 |
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| author | Vyas, Sejal Chesarone-Cataldo, Melissa Todorova, Tanya Huang, Yun-Han Chang, Paul |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Vyas, Sejal Chesarone-Cataldo, Melissa Todorova, Tanya Huang, Yun-Han Chang, Paul |
| author_sort | Vyas, Sejal |
| collection | MIT |
| description | The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD[superscript +] as their substrate to modify acceptor proteins with ADP-ribose modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyse the cell cycle localization of each PARP and of poly(ADP-ribose), a product of PARP activity, then identify the knockdown phenotype of each protein and perform secondary assays to elucidate function. We show that most PARPs are cytoplasmic, identify cell cycle differences in the ratio of nuclear to cytoplasmic poly(ADP-ribose) and identify four phenotypic classes of PARP function. These include the regulation of membrane structures, cell viability, cell division and the actin cytoskeleton. Further analysis of PARP14 shows that it is a component of focal adhesion complexes required for proper cell motility and focal adhesion function. In total, we show that PARP proteins are critical regulators of eukaryotic physiology. |
| first_indexed | 2024-09-23T11:15:59Z |
| format | Article |
| id | mit-1721.1/96281 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:15:59Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/962812022-10-01T02:25:56Z A systematic analysis of the PARP protein family identifies new functions critical for cell physiology Vyas, Sejal Chesarone-Cataldo, Melissa Todorova, Tanya Huang, Yun-Han Chang, Paul Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Chang, Paul Vyas, Sejal Chesarone-Cataldo, Melissa Todorova, Tanya Huang, Yun-Han The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD[superscript +] as their substrate to modify acceptor proteins with ADP-ribose modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyse the cell cycle localization of each PARP and of poly(ADP-ribose), a product of PARP activity, then identify the knockdown phenotype of each protein and perform secondary assays to elucidate function. We show that most PARPs are cytoplasmic, identify cell cycle differences in the ratio of nuclear to cytoplasmic poly(ADP-ribose) and identify four phenotypic classes of PARP function. These include the regulation of membrane structures, cell viability, cell division and the actin cytoskeleton. Further analysis of PARP14 shows that it is a component of focal adhesion complexes required for proper cell motility and focal adhesion function. In total, we show that PARP proteins are critical regulators of eukaryotic physiology. Rita Allen Foundation Sidney Kimmel Foundation (Cancer Research Scholar) Howard S. and Linda B. Stern Career Development Assistant Professor National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051) National Institutes of Health (U.S.) (Grant RO1GM087465) National Institutes of Health (U.S.) (Grant 1F32GM103089-01) Jeptha H. and Emily V. Wade Fund Kathy and Curt Marble Cancer Research Fund 2015-03-31T16:40:23Z 2015-03-31T16:40:23Z 2013-08 2013-04 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/96281 Vyas, Sejal, Melissa Chesarone-Cataldo, Tanya Todorova, Yun-Han Huang, and Paul Chang. “A Systematic Analysis of the PARP Protein Family Identifies New Functions Critical for Cell Physiology.” Nature Communications 4 (August 6, 2013). en_US http://dx.doi.org/10.1038/ncomms3240 Nature Communications 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 | Vyas, Sejal Chesarone-Cataldo, Melissa Todorova, Tanya Huang, Yun-Han Chang, Paul A systematic analysis of the PARP protein family identifies new functions critical for cell physiology |
| title | A systematic analysis of the PARP protein family identifies new functions critical for cell physiology |
| title_full | A systematic analysis of the PARP protein family identifies new functions critical for cell physiology |
| title_fullStr | A systematic analysis of the PARP protein family identifies new functions critical for cell physiology |
| title_full_unstemmed | A systematic analysis of the PARP protein family identifies new functions critical for cell physiology |
| title_short | A systematic analysis of the PARP protein family identifies new functions critical for cell physiology |
| title_sort | systematic analysis of the parp protein family identifies new functions critical for cell physiology |
| url | http://hdl.handle.net/1721.1/96281 |
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