Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein
The retinoblastoma tumour suppressor protein (pRb) classically functions to regulate early cell cycle progression where it acts to enforce a number of checkpoints in response to cellular stress and DNA damage. Methylation at lysine (K) 810, which occurs within a critical CDK phosphorylation site and...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2017
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| _version_ | 1826259880539848704 |
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| author | Carr, S Munro, S Sagum, C Fedorov, O Bedford, M La Thangue, N |
| author_facet | Carr, S Munro, S Sagum, C Fedorov, O Bedford, M La Thangue, N |
| author_sort | Carr, S |
| collection | OXFORD |
| description | The retinoblastoma tumour suppressor protein (pRb) classically functions to regulate early cell cycle progression where it acts to enforce a number of checkpoints in response to cellular stress and DNA damage. Methylation at lysine (K) 810, which occurs within a critical CDK phosphorylation site and antagonises a CDK-dependent phosphorylation event at the neighbouring S807 residue, acts to hold pRb in the hypo-phosphorylated growth-suppressing state. This is mediated in part by the recruitment of the reader protein 53BP1 to di-methylated K810, which allows pRb activity to be effectively integrated with the DNA damage response. Here, we report the surprising observation that an additional methylation-dependent interaction occurs at K810, but rather than the di-methyl mark, it is selective for the mono-methyl K810 mark. Binding of the mono-methyl PHF20L1 reader to methylated pRb occurs on E2F target genes, where it acts to mediate an additional level of control by recruiting the MOF acetyltransferase complex to E2F target genes. Significantly, we find that the interplay between PHF20L1 and mono-methyl pRb is important for maintaining the integrity of a pRb-dependent G1-S-phase checkpoint. Our results highlight the distinct roles that methyl-lysine readers have in regulating the biological activity of pRb.Cell Death and Differentiation advance online publication, 25 August 2017; doi:10.1038/cdd.2017.135. |
| first_indexed | 2024-03-06T18:56:48Z |
| format | Journal article |
| id | oxford-uuid:121bb1f8-cf5c-4800-ab87-5a850fc32244 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:56:48Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:121bb1f8-cf5c-4800-ab87-5a850fc322442022-03-26T10:06:01ZTudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor proteinJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:121bb1f8-cf5c-4800-ab87-5a850fc32244EnglishSymplectic Elements at OxfordSpringer Nature2017Carr, SMunro, SSagum, CFedorov, OBedford, MLa Thangue, NThe retinoblastoma tumour suppressor protein (pRb) classically functions to regulate early cell cycle progression where it acts to enforce a number of checkpoints in response to cellular stress and DNA damage. Methylation at lysine (K) 810, which occurs within a critical CDK phosphorylation site and antagonises a CDK-dependent phosphorylation event at the neighbouring S807 residue, acts to hold pRb in the hypo-phosphorylated growth-suppressing state. This is mediated in part by the recruitment of the reader protein 53BP1 to di-methylated K810, which allows pRb activity to be effectively integrated with the DNA damage response. Here, we report the surprising observation that an additional methylation-dependent interaction occurs at K810, but rather than the di-methyl mark, it is selective for the mono-methyl K810 mark. Binding of the mono-methyl PHF20L1 reader to methylated pRb occurs on E2F target genes, where it acts to mediate an additional level of control by recruiting the MOF acetyltransferase complex to E2F target genes. Significantly, we find that the interplay between PHF20L1 and mono-methyl pRb is important for maintaining the integrity of a pRb-dependent G1-S-phase checkpoint. Our results highlight the distinct roles that methyl-lysine readers have in regulating the biological activity of pRb.Cell Death and Differentiation advance online publication, 25 August 2017; doi:10.1038/cdd.2017.135. |
| spellingShingle | Carr, S Munro, S Sagum, C Fedorov, O Bedford, M La Thangue, N Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein |
| title | Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein |
| title_full | Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein |
| title_fullStr | Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein |
| title_full_unstemmed | Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein |
| title_short | Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein |
| title_sort | tudor domain protein phf20l1 reads lysine methylated retinoblastoma tumour suppressor protein |
| work_keys_str_mv | AT carrs tudordomainproteinphf20l1readslysinemethylatedretinoblastomatumoursuppressorprotein AT munros tudordomainproteinphf20l1readslysinemethylatedretinoblastomatumoursuppressorprotein AT sagumc tudordomainproteinphf20l1readslysinemethylatedretinoblastomatumoursuppressorprotein AT fedorovo tudordomainproteinphf20l1readslysinemethylatedretinoblastomatumoursuppressorprotein AT bedfordm tudordomainproteinphf20l1readslysinemethylatedretinoblastomatumoursuppressorprotein AT lathanguen tudordomainproteinphf20l1readslysinemethylatedretinoblastomatumoursuppressorprotein |