METHYLATION OF THE RETINOBLASTOMA TUMOR SUPPRESSOR BY SMYD2

SMYD2 对视网膜母细胞瘤肿瘤抑制因子的甲基化

• 批准号: 8365918
• 负责人: JULIEN SAGE
• 金额: $ 1.28万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365918
• 关键词: Acetylation; Binding; Binding Sites; Biology; Cell Cycle; Cell Cycle Progression; Cell physiology; Cells; Code; DNA Damage; Event; Funding; Fungal Genome; Grant; In Vitro; Lysine; Mammalian Cell; Methylation; Modification; National Center for Research Resources; Phosphorylation; Post-Translational Protein Processing; Principal Investigator; Research; Research Infrastructure; Resources; Site; Source; Transcription Repressor/Corepressor; Tumor Suppressor Proteins; United States National Institutes of Health; cost; novel; response; retinoblastoma tumor suppressor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The retinoblastoma tumor suppressor (RB) is a central cell cycle regulator and tumor suppressor. RB cellular functions are known to be regulated by a diversity of post-translational modifications such as phosphorylation and acetylation, raising the possibility that RB may also be methylated in cells. Here we demonstrate that RB can be methylated by SMYD2 at lysine 860, a highly conserved and novel site of modification. This methylation event occurs in vitro and in cells, and it is regulated during cell cycle progression, cellular differentiation, and in response to DNA damage. Furthermore, we show that RB monomethylation at lysine 860 provides a direct binding site for the methyl-binding domain of the transcriptional repressor L3MBTL1. These results support the idea that a code of post-translational modifications exists for RB and helps guide its functions in mammalian cells.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 视网膜母细胞瘤肿瘤抑制因子(Rb)是一种中枢细胞周期调节因子和肿瘤抑制因子。众所周知，Rb细胞的功能受多种翻译后修饰的调节，如磷酸化和乙酰化，这增加了Rb在细胞中也可能甲基化的可能性。在这里，我们证明了RB可以被位于赖氨酸860的SMYD2甲基化，这是一个高度保守的新的修饰位点。这种甲基化事件发生在体外和细胞中，它在细胞周期进程、细胞分化和对DNA损伤的反应中受到调节。此外，我们还发现Rb在赖氨酸860处的单甲基化为转录抑制物L3MBTL1的甲基结合区域提供了一个直接结合部位。这些结果支持这样的观点，即Rb存在翻译后修饰的密码，并有助于指导其在哺乳动物细胞中的功能。