期刊
ONCOTARGET
卷 6, 期 6, 页码 4005-4019出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2970
关键词
HSP90; SMYD3; tumorigenesis; lysine methylation; histone modifications
资金
- NIH [CA31534]
- Marie Betzner Morrow endowment
- Flint Animal Cancer Center
- Short Memorial Endowment
- National Science Foundation [1060548]
- Direct For Education and Human Resources
- Division Of Undergraduate Education [1060548] Funding Source: National Science Foundation
The SMYD3 histone methyl transferase (HMTase) and the nuclear chaperone, HSP90, have been independently implicated as proto-oncogenes in several human malignancies. We show that a degenerate tetratricopeptide repeat (TPR)-like domain encoded in the SMYD3 C-terminal domain (CTD) mediates physical interaction with HSP90. We further demonstrate that the CTD of SMYD3 is essential for its basal HMTase activity and that the TPR-like structure is required for HSP90-enhanced enzyme activity. Loss of SMYD3-HSP90 interaction leads to SMYD3 mislocalization within the nucleus, thereby losing its chromatin association. This results in reduction of SMYD3-mediated cell proliferation and, potentially, impairment of SMYD3's oncogenic activity. These results suggest a novel approach for blocking HSP90-driven malignancy in SMYD3-overexpressing cells with a reduced toxicity profile over current HSP90 inhibitors.
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