A conserved RAD6-MDM2 ubiquitin ligase machinery targets histone chaperone ASF1A in tumorigenesis
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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
Fang-Lin Sun, e-mail: firstname.lastname@example.org
Su Chen, e-mail: email@example.com
Xiao-Mei Yang, e-mail: firstname.lastname@example.org
Keywords: RAD6, MDM2, ASF1A, protein degradation, tumorigenesis
Received: March 06, 2015 Accepted: August 12, 2015 Published: August 22, 2015
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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