Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor

被引：42

作者：

Carr, Simon M. ^{[1
]}

Munro, Shonagh ^{[1
]}

Zalmas, Lykourgos-Panagiotis ^{[1
]}

Fedorov, Oleg ^{[2
]}

Johansson, Catrine ^{[2
]}

Krojer, Tobias ^{[2
]}

Sagum, Cari A. ^{[3
]}

Bedford, Mark T. ^{[3
]}

Oppermann, Udo ^{[2
]}

La Thangue, Nicholas B. ^{[1
]}

机构：

[1] Univ Oxford, Dept Oncol, Oxford OX3 7DQ, England

[2] Univ Oxford, Struct Genom Consortium Oxford, Oxford OX3 7DQ, England

[3] Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Smithville, TX 77030 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 31期

基金：

美国国家卫生研究院; 加拿大创新基金会; 英国医学研究理事会; 英国惠康基金;

关键词：

DNA-DAMAGE; PHOSPHORYLATION; RECOGNITION; ASSOCIATION; CHROMATIN; PATHWAY; PROTEIN; H4-K20; TUDOR; E2F;

D O I：

10.1073/pnas.1403737111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The retinoblastoma tumor suppressor protein pRb is a key regulator of cell cycle progression and mediator of the DNA damage response. Lysine methylation at K810, which occurs within a critical Cdk phosphorylation motif, holds pRb in the hypophosphorylated growth-suppressing state. We show here that methyl K810 is read by the tandem tudor domain containing tumor protein p53 binding protein 1 (53BP1). Structural elucidation of 53BP1 in complex with a methylated K810 pRb peptide emphasized the role of the 53BP1 tandem tudor domain in recognition of the methylated lysine and surrounding residues. Significantly, binding of 53BP1 to methyl K810 occurs on E2 promoter binding factor target genes and allows pRb activity to be effectively integrated with the DNA damage response. Our results widen the repertoire of cellular targets for 53BP1 and suggest a previously unidentified role for 53BP1 in regulating pRb tumor suppressor activity.

引用

页码：11341 / 11346

页数：6

共 33 条

[1]

PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].