ZSCAN4 is negatively regulated by the ubiquitin-proteasome system and the E3 ubiquitin ligase RNF20

作者: Benjamin A. Portney , Raju Khatri , W. Alex Meltzer , Jennifer M. Mariano , Michal Zalzman

DOI: 10.1016/J.BBRC.2018.02.155

关键词: Ubiquitin ligaseInduced pluripotent stem cellStem cellProteasomeUbiquitinChemistryGene knockdownCell biologyEmbryonic stem cellProtein degradation

摘要: Zscan4 is an early embryonic gene cluster expressed in mouse stem and induced pluripotent cells where it plays critical roles genomic stability, telomere maintenance, pluripotency. expression transient, characterized by infrequent high peaks that are quickly down-regulated, suggesting its tightly controlled. However, little known about the protein degradation pathway responsible for regulating human ZSCAN4 levels. In this study we determine first time half-life pathway, including key factors involved process, regulation of stability. We demonstrate lysine 48 specific polyubiquitination subsequent proteasome dependent ZSCAN4, which may explain how factor efficiently cleared from cells. Importantly, our data indicate interaction between E3 ubiquitin ligase RNF20. Moreover, results show RNF20 depletion knockdown does not affect transcription levels, but instead increased Further, stabilizes half-life, negatively regulates Due to significant cellular functions have important implications regulation, cell biology, cancer.

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