Polycomb group (PcG) proteins regulate transcription, playing a key role in stemness and differentiation. Deregulation of PcG members is known to be involved in cancer pathogenesis. Emerging evidence suggests that CBX2, a member of the PcG protein family, is overexpressed in several human tumors, correlating with lower overall survival. Unraveling the mechanisms regulating CBX2 expression may thus provide a promising new target for anticancer strategies. Here we show that the HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin-mediated pathway in leukemia. We identify CBX4 and RNF4 as the E3 SUMO and E3 ubiquitin ligase, respectively, and describe the specific molecular mechanism regulating CBX2 protein stability. Finally, we show that CBX2-depleted leukemic cells display impaired proliferation, underscoring its critical role in regulating leukemia cell tumorogenicity. Our results show that SAHA affects CBX2 stability, revealing a potential SAHA-mediated anti-leukemic activity though SUMO2/3 pathway.

中文翻译：

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HDAC抑制剂SAHA通过SUMO触发的泛素介导的白血病途径调节CBX2的稳定性。

Polycomb group（PcG）蛋白调节转录，在茎干和分化中起关键作用。众所周知，PcG成员的失调与癌症的发病机理有关。新兴证据表明，CbX2是PcG蛋白家族的成员，在几种人类肿瘤中均过表达，与较低的总体生存率相关。阐明调节CBX2表达的机制可能因此为抗癌策略提供有希望的新靶标。在这里，我们显示HDAC抑制剂SAHA通过SUMO触发的遍在蛋白介导的白血病途径调节CBX2稳定性。我们分别确定CBX4和RNF4为E3 SUMO和E3泛素连接酶，并描述调节CBX2蛋白稳定性的特定分子机制。最后，我们显示CBX2耗竭的白血病细胞显示出受损的增殖，强调其在调节白血病细胞致瘤性中的关键作用。我们的结果表明，SAHA影响CBX2的稳定性，通过SUMO2 / 3途径揭示了潜在的SAHA介导的抗白血病活性。