Tanaskovic Nina, Dalsass Mattia, Filipuzzi Marco, Ceccotti Giorgia, Verrecchia Alessandro, Nicoli Paola, Doni Mirko, Olivero Daniela, Pasini Diego, Koseki Haruhiko, Sabò Arianna, Bisso Andrea, Amati Bruno
European Institute of Oncology (IEO) - IRCCS, Milan, Italy.
Laboratorio Analisi Veterinarie BiEsseA, A Company of Scil Animal Care Company Srl, Milan, Italy.
Life Sci Alliance. 2022 Apr 14;5(8). doi: 10.26508/lsa.202101344. Print 2022 Aug.
Max is an obligate dimerization partner for the Myc transcription factors and for several repressors, such as Mnt, Mxd1-4, and Mga, collectively thought to antagonize Myc function in transcription and oncogenesis. Mga, in particular, is part of the variant Polycomb group repressive complex PRC1.6. Here, we show that ablation of the distinct PRC1.6 subunit Pcgf6-but not Mga-accelerates Myc-induced lymphomagenesis in Eµ- transgenic mice. Unexpectedly, however, Pcgf6 loss shows no significant impact on transcriptional profiles, in neither pre-tumoral B-cells, nor lymphomas. Altogether, these data unravel an unforeseen, Mga- and PRC1.6-independent tumor suppressor activity of Pcgf6.
Max是Myc转录因子以及多种阻遏蛋白(如Mnt、Mxd1 - 4和Mga)的必需二聚化伙伴,这些蛋白被认为共同拮抗Myc在转录和肿瘤发生中的功能。特别是Mga,它是变体多梳蛋白组抑制复合物PRC1.6的一部分。在此,我们表明,在Eµ - 转基因小鼠中,敲除独特的PRC1.6亚基Pcgf6而非Mga,会加速Myc诱导的淋巴瘤发生。然而,出乎意料的是,Pcgf6缺失对肿瘤前B细胞和淋巴瘤的转录谱均无显著影响。总之,这些数据揭示了Pcgf6一种前所未有的、不依赖Mga和PRC1.6的肿瘤抑制活性。