The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans
The extant jawless vertebrates, represented by lampreys and hagfish, are the oldest group of vertebrates and provide an interesting genomic evolutionary pivot point between invertebrates and jawed vertebrates. Through genome analysis of one of these jawless vertebrates, the Japanese lamprey (Lethent...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2016
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/82782 http://hdl.handle.net/10220/40297 |
| _version_ | 1826120151997612032 |
|---|---|
| author | Venkatesh, Byrappa Lane, David P. Coffill, Cynthia R. Lee, Alison P. Siau, Jia Wei Chee, Sharon M. Joseph, Thomas L. Tan, Yaw Sing Madhumalar, Arumugam Tay, Boon-Hui Brenner, Sydney Verma, Chandra Shekhar Ghadessy, Farid J. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Venkatesh, Byrappa Lane, David P. Coffill, Cynthia R. Lee, Alison P. Siau, Jia Wei Chee, Sharon M. Joseph, Thomas L. Tan, Yaw Sing Madhumalar, Arumugam Tay, Boon-Hui Brenner, Sydney Verma, Chandra Shekhar Ghadessy, Farid J. |
| author_sort | Venkatesh, Byrappa |
| collection | NTU |
| description | The extant jawless vertebrates, represented by lampreys and hagfish, are the oldest group of vertebrates and provide an interesting genomic evolutionary pivot point between invertebrates and jawed vertebrates. Through genome analysis of one of these jawless vertebrates, the Japanese lamprey (Lethenteron japonicum), we identified all three members of the important p53 transcription factor family—Tp53, Tp63, and Tp73—as well as the Mdm2 and Mdm4 genes. These genes and their products are significant cellular regulators in human cancer, and further examination of their roles in this most distant vertebrate relative sheds light on their origin and coevolution. Their important role in response to DNA damage has been highlighted by the discovery of multiple copies of the Tp53 gene in elephants. Expression of lamprey p53, Mdm2, and Mdm4 proteins in mammalian cells reveals that the p53–Mdm2 interaction and the Mdm2/Mdm4 E3 ligase activity existed in the common ancestor of vertebrates and have been conserved for >500 million years of vertebrate evolution. Lamprey Mdm2 degrades human p53 with great efficiency, but this interaction is not blocked by currently available small molecule inhibitors of the human HDM2 protein, suggesting utility of lamprey Mdm2 in the study of the human p53 signaling pathway. |
| first_indexed | 2024-10-01T05:11:50Z |
| format | Journal Article |
| id | ntu-10356/82782 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:11:50Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/827822023-02-28T16:56:04Z The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans Venkatesh, Byrappa Lane, David P. Coffill, Cynthia R. Lee, Alison P. Siau, Jia Wei Chee, Sharon M. Joseph, Thomas L. Tan, Yaw Sing Madhumalar, Arumugam Tay, Boon-Hui Brenner, Sydney Verma, Chandra Shekhar Ghadessy, Farid J. School of Biological Sciences P53 Mdm2 Mdm4 Evolution Lamprey The extant jawless vertebrates, represented by lampreys and hagfish, are the oldest group of vertebrates and provide an interesting genomic evolutionary pivot point between invertebrates and jawed vertebrates. Through genome analysis of one of these jawless vertebrates, the Japanese lamprey (Lethenteron japonicum), we identified all three members of the important p53 transcription factor family—Tp53, Tp63, and Tp73—as well as the Mdm2 and Mdm4 genes. These genes and their products are significant cellular regulators in human cancer, and further examination of their roles in this most distant vertebrate relative sheds light on their origin and coevolution. Their important role in response to DNA damage has been highlighted by the discovery of multiple copies of the Tp53 gene in elephants. Expression of lamprey p53, Mdm2, and Mdm4 proteins in mammalian cells reveals that the p53–Mdm2 interaction and the Mdm2/Mdm4 E3 ligase activity existed in the common ancestor of vertebrates and have been conserved for >500 million years of vertebrate evolution. Lamprey Mdm2 degrades human p53 with great efficiency, but this interaction is not blocked by currently available small molecule inhibitors of the human HDM2 protein, suggesting utility of lamprey Mdm2 in the study of the human p53 signaling pathway. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2016-03-18T03:17:23Z 2019-12-06T15:05:27Z 2016-03-18T03:17:23Z 2019-12-06T15:05:27Z 2016 Journal Article Coffill, C. R., Lee, A. P., Siau, J. W., Chee, S. M., Joseph, T. L., Tan, Y. S., et al. (2016). The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans. Genes & Development, 30, 281-292. 0890-9369 https://hdl.handle.net/10356/82782 http://hdl.handle.net/10220/40297 10.1101/gad.274118.115 26798135 en Genes & Development © 2016 Coffill et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. 13 p. application/pdf |
| spellingShingle | P53 Mdm2 Mdm4 Evolution Lamprey Venkatesh, Byrappa Lane, David P. Coffill, Cynthia R. Lee, Alison P. Siau, Jia Wei Chee, Sharon M. Joseph, Thomas L. Tan, Yaw Sing Madhumalar, Arumugam Tay, Boon-Hui Brenner, Sydney Verma, Chandra Shekhar Ghadessy, Farid J. The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans |
| title | The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans |
| title_full | The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans |
| title_fullStr | The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans |
| title_full_unstemmed | The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans |
| title_short | The p53–Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans |
| title_sort | p53 mdm2 interaction and the e3 ligase activity of mdm2 mdm4 are conserved from lampreys to humans |
| topic | P53 Mdm2 Mdm4 Evolution Lamprey |
| url | https://hdl.handle.net/10356/82782 http://hdl.handle.net/10220/40297 |
| work_keys_str_mv | AT venkateshbyrappa thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT lanedavidp thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT coffillcynthiar thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT leealisonp thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT siaujiawei thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT cheesharonm thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT josephthomasl thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT tanyawsing thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT madhumalararumugam thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT tayboonhui thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT brennersydney thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT vermachandrashekhar thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT ghadessyfaridj thep53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT venkateshbyrappa p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT lanedavidp p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT coffillcynthiar p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT leealisonp p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT siaujiawei p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT cheesharonm p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT josephthomasl p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT tanyawsing p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT madhumalararumugam p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT tayboonhui p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT brennersydney p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT vermachandrashekhar p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans AT ghadessyfaridj p53mdm2interactionandthee3ligaseactivityofmdm2mdm4areconservedfromlampreystohumans |