Unit of Gene Therapy and Stem Cell Biology, Department of Ophtalmology, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland.
Adv Exp Med Biol. 2018;1074:359-365. doi: 10.1007/978-3-319-75402-4_44.
Retinitis Pigmentosa (RP) is a class of hereditary retinal dystrophy associated with gradual visual failure and a subsequent loss of light-sensitive cells in the retina, leading to blindness. Many mutated genes were found to be causative of this disease. Despite a number of compiling efforts, the process of cell death in photoreceptors remains to be clearly elucidated. We recently reported an abnormal cell cycle reentry in photoreceptors undergoing degeneration in Rd1 mice, a model of RP, and identified the polycomb repressive complex 1 (PRC1) core component BMI1 as a critical molecular factor orchestrating the cell death mechanism. As the cell death rescue in Rd1;Bmi-1 KO mice was independent on the conventional Ink4a/Arf pathways, we now explored the structural properties of BMI1 in order to examine the differential expression of its posttranslational modifications in Rd1 retina. Our results suggest that BMI1 cell death induction in Rd1 is not related to its phosphorylation status. We therefore propose the epigenetic activity of BMI1 as an alternative route for BMI1-mediated toxicity in Rd1.
色素性视网膜炎（RP）是一类与视力逐渐丧失和视网膜感光细胞随后丧失相关的遗传性视网膜变性，导致失明。许多突变基因被发现是导致这种疾病的原因。尽管进行了许多编纂工作，但感光细胞的细胞死亡过程仍未得到明确阐明。我们最近在 RP 模型 Rd1 小鼠的变性感光细胞中报告了异常的细胞周期重新进入，并确定多梳抑制复合物 1（PRC1）核心成分 BMI1 是协调细胞死亡机制的关键分子因素。由于 Rd1;Bmi-1 KO 小鼠中的细胞死亡挽救不依赖于传统的 Ink4a/Arf 途径，因此我们现在研究了 BMI1 的结构特性，以检查 Rd1 视网膜中其翻译后修饰的差异表达。我们的结果表明，Rd1 中 BMI1 的细胞死亡诱导与它的磷酸化状态无关。因此，我们提出 BMI1 的表观遗传活性作为 Rd1 中 BMI1 介导的毒性的另一种途径。
