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

作者：Wang Chen; Chang Jian Feng; Yan Hongli; Wang Da Liang; Liu Yan; Jing Yuanya; Zhang Meng; Men Yu Long; Lu Dongdong; Yang Xiao Mei; Chen Su; Sun Fang Lin^*

来源：Oncotarget, 2015, 6(30): 29599-29613.

DOI：10.18632/oncotarget.5011

• RAD6
• MDM2
• ASF1A
• protein degradation
• tumorigenesis

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.

• 出版日期2015-10-6
• 单位清华大学; 同济大学; 中国人民解放军第二军医大学