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

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Bibliographic Details
Published in:Oncotarget 2015-10, Vol.6 (30), p.29599-29613
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Line
Cell Line, Tumor
Drosophila melanogaster - cytology
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Gene Expression Regulation, Neoplastic
HEK293 Cells
Hep G2 Cells
Histones - metabolism
Humans
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Microscopy, Confocal
Molecular Chaperones - genetics
Molecular Chaperones - metabolism
Proto-Oncogene Proteins c-mdm2 - genetics
Proto-Oncogene Proteins c-mdm2 - metabolism
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Ubiquitin-Conjugating Enzymes - genetics
Ubiquitin-Conjugating Enzymes - metabolism
Ubiquitination
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.5011