Cocco Lucio, Follo Matilde Y, Faenza Irene, Fiume Roberta, Ramazzotti Giulia, Weber George, Martelli Alberto M, Manzoli Francesco A
Cellular Signalling Laboratory, Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy.
Adv Enzyme Regul. 2011;51(1):2-12. doi: 10.1016/j.advenzreg.2010.09.015. Epub 2010 Oct 28.
The existence and function of inositide signaling in the nucleus is well documented and we know that the existence of the inositide cycle inside the nucleus has a biological role. An autonomous lipid-dependent signaling system, independently regulated from its plasma membrane counterpart, acts in the nucleus and modulates cell cycle progression and differentiation.We and others focused on PLCβ1, which is the most extensively investigated PLC isoform in the nuclear compartment. PLCβ1 is a key player in the regulation of nuclear inositol lipid signaling, and, as discussed above, its function could also be involved in nuclear structure because it hydrolyses PtdIns(4,5)P2, a well accepted regulator of chromatin remodelling. The evidence, in a number of patients with myelodysplastic syndromes, that the mono-allelic deletion of PLCβ1 is associated with an increased risk of developing acute myeloid leukemia paves the way for an entirely new field of investigation. Indeed the genetic defect evidenced, in addition to being a useful prognostic tool, also suggests that altered expression of this enzyme could have a role in the pathogenesis of this disease, by causing an imbalance between proliferation and apoptosis. The epigenetics of PLCβ1 expression in MDS has been reviewed as well.
细胞核中肌醇磷脂信号传导的存在及其功能已有充分记载，并且我们知道细胞核内肌醇磷脂循环的存在具有生物学作用。一种独立于质膜对应系统的自主脂质依赖性信号系统在细胞核中发挥作用，并调节细胞周期进程和分化。我们和其他研究人员聚焦于PLCβ1，它是在核区室中研究最为广泛的PLC亚型。PLCβ1是调节细胞核肌醇脂质信号传导的关键因子，并且如上所述，其功能也可能与核结构有关，因为它能水解磷脂酰肌醇 - 4,5 - 二磷酸（PtdIns(4,5)P2），这是一种公认的染色质重塑调节因子。在一些骨髓增生异常综合征患者中，PLCβ1单等位基因缺失与急性髓系白血病发生风险增加相关，这一证据为一个全新的研究领域铺平了道路。事实上，所证实的基因缺陷不仅是一种有用的预后工具还表明，该酶表达的改变可能通过导致增殖与凋亡之间的失衡而在这种疾病的发病机制中起作用。骨髓增生异常综合征中PLCβ1表达的表观遗传学也已得到综述。
