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

Oncotarget
Chen WangFang-Lin Sun

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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Citations

Jul 10, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Fei QiuJing Wang
Nov 27, 2019·Genes·Madhumitha Kedhari SundaramShafiul Haque
Mar 31, 2018·Nature Communications·Shangda YangLei Shi
Feb 13, 2021·Personalized Medicine·Zhenxing FengTieshuan Tian

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Methods Mentioned

BETA
acetylation
two-hybrid
co-immunoprecipitation
Co-IP
ubiquitination
co-immunoprecipitation assay
immunoprecipitation
pull down
pull-down
nuclear translocation

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