Oncotarget

Research Papers:

A conserved RAD6-MDM2 ubiquitin ligase machinery targets histone chaperone ASF1A in tumorigenesis

Chen Wang _, Jian-Feng Chang, Hongli Yan, Da-Liang Wang, Yan Liu, Yuanya Jing, Meng Zhang, Yu-Long Men, Dongdong Lu, Xiao-Mei Yang, Su Chen and Fang-Lin Sun

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Oncotarget. 2015; 6:29599-29613. https://doi.org/10.18632/oncotarget.5011

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Abstract

Chen Wang1,2,3,*, Jian-Feng Chang1,2,*, Hongli Yan4,*, Da-Liang Wang5, Yan Liu5, Yuanya Jing2, Meng Zhang2, Yu-Long Men2, Dongdong Lu2, Xiao-Mei Yang2, Su Chen1,2,6, Fang-Lin Sun1,2

1Research Center for Translational Medicine at East Hospital, Tongji University, Shanghai, 200120/200092, China

2School of Life Sciences and Technology, Tongji University, Shanghai, 200120/200092, China

3UN School of Environmental Sciences and Technology, Tongji University, Shanghai, 200120/200092, China

4Department of Laboratory Medicine, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China

5Institute of Epigenetics and Cancer Research, School of Medicine, Tsinghua University, Beijing, 100084, China

6Department of Science and Education, People’s Hospital of Zunhua, Tangshan, Hebei, 064200, China

*These authors have contributed equally to this work

Correspondence to:

Fang-Lin Sun, e-mail: sfl@tongji.edu.cn

Su Chen, e-mail: chensu@tongji.edu.cn

Xiao-Mei Yang, e-mail: yxm411@tongji.edu.cn

Keywords: RAD6, MDM2, ASF1A, protein degradation, tumorigenesis

Received: March 06, 2015     Accepted: August 12, 2015     Published: August 22, 2015

ABSTRACT

Chromatin is a highly organized and dynamic structure in eukaryotic cells. The change of chromatin structure is essential in many cellular processes, such as gene transcription, DNA damage repair and others. Anti-silencing function 1 (ASF1) is a histone chaperone that participates in chromatin higher-order organization and is required for appropriate chromatin assembly. In this study, we identified the E2 ubiquitin-conjugating enzyme RAD6 as an evolutionary conserved interacting protein of ASF1 in D. melanogaster and H. sapiens that promotes the turnover of ASF1A by cooperating with a well-known E3 ligase, MDM2, via ubiquitin-proteasome pathway in H. sapiens. Further functional analyses indicated that the interplay between RAD6 and ASF1A associates with tumorigenesis. Together, these data suggest that the RAD6-MDM2 ubiquitin ligase machinery is critical for the degradation of chromatin-related proteins.


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