Bimodal Regulation of the PRC2 Complex by USP7 Underlies Melanomagenesis

Abstract

Although overexpression of EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is an eminent feature of various cancers, the regulation of its abundance and function remains insufficiently understood. We report here that the PRC2 complex is physically associated with ubiquitin-specific protease USP7 in melanoma cells where USP7 acts to deubiquitinate and stabilize EZH2. Interestingly, we found that USP7-catalyzed H2BK120 deubiquitination is a prerequisite for chromatin loading of PRC2 thus H3K27 trimethylation.Genome-wide analysis of the transcriptional targets of the USP7/PRC2 complex identified a cohort of genes including FOXO1 that are involved in cell growth and proliferation. We demonstrated that the USP7/PRC2 complex drives melanoma cell proliferation and tumorigenesis in vitro and in vivo. We showed that the expression of both USP7 and EZH2 elevates during melanoma progression, corresponding to a diminished FOXO1 expression, and the level of the expression of USP7 and EZH2 strongly correlates with histological grades and prognosis of melanoma patients. These results reveal a dual role for USP7 in the regulation of the abundance and function of EZH2, supporting the pursuit of USP7 as a therapeutic target for melanoma.

The Improved Microwave Absorption Performance of the 3D Porous (Ni@NO-C)n/No-C Composite Absorber

“…As a matter of fact, the nine peaks observed in Figure 5c are indicative of various ferromagnetic resonance modes. The relatively sharp resonance peaks between 2.0 and 11.0 GHz are attributed to the natural resonance from static magnetic energy, while the relatively broad resonance peaks between 11.0 and 18.0 GHz belong to exchange resonance among different magnetic nanoparticles [40]. It is widely accepted that natural resonance is affected by the inherent properties of the material itself, such as size, morphology and other factors.…”

“…The multiple natural resonances of (Ni@NO-C)n/NO-C can be attributed to the discrete distributions of different-sized NO-C encapsulated Ni@NO-C nanoparticles or their (Ni@NO-C)n chains. On the other hand, exchange resonance is usually associated with spin-wave excitations, small size effect, and surface effect of small-size magnetic nanoparticles in the higher frequency range [40]. For the as-prepared (Ni@NO-C)n/NO-C EM absorbent, the Ni cores (or short Ni chains) are insulated by nitrogen and oxygen codoped graphite layers, which can intensely suppress the eddy current effect.…”