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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
PRAJA1 is a ubiquitin ligase for the polycomb repressive complex 2 proteins
Muhammad Zoabi1, Ronen Sadeh, Prim de Bie
1Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Biochemical and Biophysical Research Communications
|April 26, 2011
Summary
Polycomb Repressive Complex 2 (PRC2) subunits are degraded via the ubiquitin-proteasome system. The E3 ubiquitin ligase PRAJA1 targets PRC2 subunits, regulating PRC2 levels.
Area of Science:
- Epigenetics
- Gene Regulation
- Molecular Biology
Background:
- Polycomb Repressive Complex 2 (PRC2) mediates gene silencing through histone H3 lysine 27 methylation.
- PRC2 core subunits (EZH2, EED, SUZ12) are interdependent and degraded by the ubiquitin-proteasome system (UPS).
- Inhibition of methyltransferases with DZNep causes PRC2 dissociation and degradation, inducing ubiquitin ligases.
Purpose of the Study:
- To investigate the role of DZNep-induced ubiquitin ligases in PRC2 subunit degradation.
- To identify specific ubiquitin ligases targeting PRC2 subunits.
- To elucidate the mechanism of PRAJA1 in regulating PRC2 stability.
Main Methods:
- Confirmation of PRC2 subunit ubiquitination and proteasomal degradation.
- Identification and characterization of PRAJA1 as a PRC2-targeting ubiquitin ligase.
- In vitro ubiquitination assays and cell-based degradation studies.
Main Results:
- Individual PRC2 subunits are ubiquitinated and degraded by the proteasome.
- PRAJA1 directly ubiquitinates PRC2 subunits, leading to their degradation.
- PRAJA1 expression enhances PRC2 subunit degradation in cells.
Conclusions:
- PRAJA1 targets free PRC2 subunits for ubiquitin-mediated proteasomal degradation.
- PRAJA1 plays a crucial role in regulating PRC2 protein levels.
- This mechanism provides insight into the dynamic regulation of epigenetic modifiers.
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