期刊
CELL DEATH AND DIFFERENTIATION
卷 24, 期 12, 页码 2139-2149出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2017.135
关键词
-
资金
- Cancer Prevention Research Institute of Texas funding [RP110471]
- Cancer Research UK Programme Award [300/A13058]
- Canada Foundation for Innovation
- Research Council (MRC) grant
- CPRIT grant [PR130432]
- Eli Lilly
- Takeda
- AbbVie
- Novartis Research Foundation
- Ontario Ministry of Research and Innovation
- Rosetrees Trust
- Structural Genomics Consortium from the Canadian Institute for Health Research [1097737]
- National Institutes of Health Grant [DK062248]
- Genome Canada
- Wellcome Trust [092809/Z/10/Z]
- GlaxoSmithKline
- Pfizer
- BBSRC [BB/P009212/1] Funding Source: UKRI
- MRC [G9400953, G1000807, G0500905] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/P009212/1] Funding Source: researchfish
- Cancer Research UK [20776, 13058] Funding Source: researchfish
- Medical Research Council [G1000807, G0500905, 1382296, G9400953] Funding Source: researchfish
- Rosetrees Trust [M271-F1, M271-F2] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据