Family-wide analysis of poly(ADP-ribose) polymerase activity
The poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD[superscript +] as substrate. Based on the composition of three NAD[superscript +] coordinating amino acids, the H-Y-E motif, each PARP is predict...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/96282 https://orcid.org/0000-0001-5253-8185 |
| _version_ | 1811079077449170944 |
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| author | Vyas, Sejal Matic, Ivan Uchima, Lilen Rood, Jenny Zaja, Roko Hay, Ronald T. Ahel, Ivan Chang, Paul |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Vyas, Sejal Matic, Ivan Uchima, Lilen Rood, Jenny Zaja, Roko Hay, Ronald T. Ahel, Ivan Chang, Paul |
| author_sort | Vyas, Sejal |
| collection | MIT |
| description | The poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD[superscript +] as substrate. Based on the composition of three NAD[superscript +] coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADPr) (PAR) or mono(ADPr) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms. Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. In addition, we identify cysteine as a novel amino-acid target for ADP-ribosylation on PARPs. |
| first_indexed | 2024-09-23T11:09:41Z |
| format | Article |
| id | mit-1721.1/96282 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:09:41Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/962822022-09-27T17:32:12Z Family-wide analysis of poly(ADP-ribose) polymerase activity Vyas, Sejal Matic, Ivan Uchima, Lilen Rood, Jenny Zaja, Roko Hay, Ronald T. Ahel, Ivan Chang, Paul Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Vyas, Sejal Uchima, Lilen Rood, Jenny Chang, Paul The poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD[superscript +] as substrate. Based on the composition of three NAD[superscript +] coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADPr) (PAR) or mono(ADPr) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms. Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. In addition, we identify cysteine as a novel amino-acid target for ADP-ribosylation on PARPs. Rita Allen Foundation Sidney Kimmel Foundation National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051) National Institutes of Health (U.S.) (Grant RO1GM087465) Kathy and Curt Marble Cancer Research Fund Wellcome Trust (London, England) European Research Council 2015-03-31T16:49:32Z 2015-03-31T16:49:32Z 2014-07 2014-02 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/96282 Vyas, Sejal, Ivan Matic, Lilen Uchima, Jenny Rood, Roko Zaja, Ronald T. Hay, Ivan Ahel, and Paul Chang. “Family-Wide Analysis of poly(ADP-Ribose) Polymerase Activity.” Nature Communications 5 (July 21, 2014). https://orcid.org/0000-0001-5253-8185 en_US http://dx.doi.org/10.1038/ncomms5426 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 Matic, Ivan Uchima, Lilen Rood, Jenny Zaja, Roko Hay, Ronald T. Ahel, Ivan Chang, Paul Family-wide analysis of poly(ADP-ribose) polymerase activity |
| title | Family-wide analysis of poly(ADP-ribose) polymerase activity |
| title_full | Family-wide analysis of poly(ADP-ribose) polymerase activity |
| title_fullStr | Family-wide analysis of poly(ADP-ribose) polymerase activity |
| title_full_unstemmed | Family-wide analysis of poly(ADP-ribose) polymerase activity |
| title_short | Family-wide analysis of poly(ADP-ribose) polymerase activity |
| title_sort | family wide analysis of poly adp ribose polymerase activity |
| url | http://hdl.handle.net/1721.1/96282 https://orcid.org/0000-0001-5253-8185 |
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