Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage
Pellino1 is an E3 ubiquitin ligase that plays a key role in positive regulation of innate immunity signaling, specifically required for the production of interferon when induced by viral double-stranded RNA. We report the identification of the tumor suppressor protein, p53, as a binding partner of P...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/151627 |
| _version_ | 1826116438321004544 |
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| author | Dai, Liang Lin, Jianqing Aminahtusaidah Said Yau, Yin Hoe Shochat, Susana Geifman Ruiz-Carrillo, David Sun, Kang Chandrasekaran, Ramya Sze, Siu Kwan Lescar, Julien Cheung, Peter Ching For |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Dai, Liang Lin, Jianqing Aminahtusaidah Said Yau, Yin Hoe Shochat, Susana Geifman Ruiz-Carrillo, David Sun, Kang Chandrasekaran, Ramya Sze, Siu Kwan Lescar, Julien Cheung, Peter Ching For |
| author_sort | Dai, Liang |
| collection | NTU |
| description | Pellino1 is an E3 ubiquitin ligase that plays a key role in positive regulation of innate immunity signaling, specifically required for the production of interferon when induced by viral double-stranded RNA. We report the identification of the tumor suppressor protein, p53, as a binding partner of Pellino1. Their interaction has a K𝘥 of 42 ± 2 μM and requires phosphorylation of Thr18 within p53 and association with the forkhead-associated (FHA) domain of Pellino1. We employed laser micro-irradiation and live cell microscopy to show that Pellino1 is recruited to newly occurring DNA damage sites, via its FHA domain. Mutation of a hitherto unidentified nuclear localization signal within the N-terminus of Pellino1 led to its exclusion from the nucleus. This study provides evidence that Pellino1 translocates to damaged DNA in the nucleus and has a functional role in p53 signaling and the DNA damage response. |
| first_indexed | 2024-10-01T04:11:44Z |
| format | Journal Article |
| id | ntu-10356/151627 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:11:44Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1516272021-07-01T07:11:01Z Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage Dai, Liang Lin, Jianqing Aminahtusaidah Said Yau, Yin Hoe Shochat, Susana Geifman Ruiz-Carrillo, David Sun, Kang Chandrasekaran, Ramya Sze, Siu Kwan Lescar, Julien Cheung, Peter Ching For School of Biological Sciences Nanyang Institute of Structural Biology Science::Biological sciences Pellino1 p53 Pellino1 is an E3 ubiquitin ligase that plays a key role in positive regulation of innate immunity signaling, specifically required for the production of interferon when induced by viral double-stranded RNA. We report the identification of the tumor suppressor protein, p53, as a binding partner of Pellino1. Their interaction has a K𝘥 of 42 ± 2 μM and requires phosphorylation of Thr18 within p53 and association with the forkhead-associated (FHA) domain of Pellino1. We employed laser micro-irradiation and live cell microscopy to show that Pellino1 is recruited to newly occurring DNA damage sites, via its FHA domain. Mutation of a hitherto unidentified nuclear localization signal within the N-terminus of Pellino1 led to its exclusion from the nucleus. This study provides evidence that Pellino1 translocates to damaged DNA in the nucleus and has a functional role in p53 signaling and the DNA damage response. Agency for Science, Technology and Research (A*STAR) This research was supported by Academic Research Fund Tier 1 (Singapore) grant 2014-T1-001-274 (RG53/14) to PCFC and BMRC (Singapore) grant 0912219/599 to JL. 2021-07-01T07:11:01Z 2021-07-01T07:11:01Z 2019 Journal Article Dai, L., Lin, J., Aminahtusaidah Said, Yau, Y. H., Shochat, S. G., Ruiz-Carrillo, D., Sun, K., Chandrasekaran, R., Sze, S. K., Lescar, J. & Cheung, P. C. F. (2019). Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage. Biochemical and Biophysical Research Communications, 513(3), 714-720. https://dx.doi.org/10.1016/j.bbrc.2019.03.095 0006-291X https://hdl.handle.net/10356/151627 10.1016/j.bbrc.2019.03.095 30987826 2-s2.0-85064169728 3 513 714 720 en 2014-T1-001-274 (RG53/14) 0912219/599 Biochemical and Biophysical Research Communications © 2019 Elsevier Inc. All rights reserved. |
| spellingShingle | Science::Biological sciences Pellino1 p53 Dai, Liang Lin, Jianqing Aminahtusaidah Said Yau, Yin Hoe Shochat, Susana Geifman Ruiz-Carrillo, David Sun, Kang Chandrasekaran, Ramya Sze, Siu Kwan Lescar, Julien Cheung, Peter Ching For Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage |
| title | Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage |
| title_full | Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage |
| title_fullStr | Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage |
| title_full_unstemmed | Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage |
| title_short | Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage |
| title_sort | pellino1 specifically binds to phospho thr18 of p53 and is recruited to sites of dna damage |
| topic | Science::Biological sciences Pellino1 p53 |
| url | https://hdl.handle.net/10356/151627 |
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