Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53

Qi Fei, Ke Shang, Jianhua Zhang, Shannon Chuai, Desheng Kong, Tianlun Zhou, Shijun Fu, Ying Liang, Chong Li, Zhi Chen, Yuan Zhao, Zhengtian Yu, Zheng Huang, Min Hu, Haiyan Ying, Zhui Chen, Yun Zhang, Feng Xing, Jidong Zhu, Haiyan Xu, Kehao Zhao, Chris Lu, Peter Atadja, Zhi-Xiong Xiao, En Li and Jianyong Shou ()
Additional contact information
Qi Fei: Novartis Institutes for BioMedical Research
Ke Shang: Novartis Institutes for BioMedical Research
Jianhua Zhang: Novartis Institutes for BioMedical Research
Shannon Chuai: Novartis Institutes for BioMedical Research
Desheng Kong: Novartis Institutes for BioMedical Research
Tianlun Zhou: Novartis Institutes for BioMedical Research
Shijun Fu: Novartis Institutes for BioMedical Research
Ying Liang: Novartis Institutes for BioMedical Research
Chong Li: Novartis Institutes for BioMedical Research
Zhi Chen: Novartis Institutes for BioMedical Research
Yuan Zhao: Novartis Institutes for BioMedical Research
Zhengtian Yu: Novartis Institutes for BioMedical Research
Zheng Huang: Novartis Institutes for BioMedical Research
Min Hu: Novartis Institutes for BioMedical Research
Haiyan Ying: Novartis Institutes for BioMedical Research
Zhui Chen: Novartis Institutes for BioMedical Research
Yun Zhang: Novartis Institutes for BioMedical Research
Feng Xing: Novartis Institutes for BioMedical Research
Jidong Zhu: Novartis Institutes for BioMedical Research
Haiyan Xu: Novartis Institutes for BioMedical Research
Kehao Zhao: Novartis Institutes for BioMedical Research
Chris Lu: Novartis Institutes for BioMedical Research
Peter Atadja: Novartis Institutes for BioMedical Research
Zhi-Xiong Xiao: College of Life Sciences, Sichuan University
En Li: Novartis Institutes for BioMedical Research
Jianyong Shou: Novartis Institutes for BioMedical Research

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract SETDB1 is a histone H3K9 methyltransferase that has a critical role in early development. It is located within a melanoma susceptibility locus and facilitates melanoma formation. However, the mechanism by which SETDB1 regulates tumorigenesis remains unknown. Here we report the molecular interplay between SETDB1 and the well-known hotspot gain-of-function (GOF) TP53 R249S mutation. We show that in hepatocellular carcinoma (HCC) SETDB1 is overexpressed with moderate copy number gain, and GOF TP53 mutations including R249S associate with this overexpression. Inactivation of SETDB1 in HCC cell lines bearing the R249S mutation suppresses cell growth. The TP53 mutation status renders cancer cells dependent on SETDB1. Moreover, SETDB1 forms a complex with p53 and catalyses p53K370 di-methylation. SETDB1 attenuation reduces the p53K370me2 level, which subsequently leads to increased recognition and degradation of p53 by MDM2. Together, we provide both genetic and biochemical evidence for a mechanism by which SETDB1 regulates cancer cell growth via methylation of p53.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms9651 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9651

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9651

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().