Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 45137-66731, Iran; Research Center for Basic Sciences and Modern Technologies (RBST), Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 45137-66731, Iran.
Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 45137-66731, Iran.
Eur J Pharmacol. 2019 Jul 15;855:20-29. doi: 10.1016/j.ejphar.2019.04.048. Epub 2019 Apr 30.
Cellular differentiation is one of the critical processes in the life of multicellular organisms. In this phenomenon, a non-specialized cell is converted to a specialized one with its own specific function and morphology. One of the requirements for specialization is silencing of the pathways involved in cell proliferation in parallel with turning on the molecular mechanisms involved in differentiation. Similar to other biological phenomena, the change in cellular state from the proliferative to the differentiated needs molecular switches to persuade the change in response to the internal or external inducers. The quiddity of these molecular switches has not been identified, yet. However, there exists a growing body of evidence showing that the same agents involved in apoptosis have a broad contribution to differentiation progression. To our knowledge, this evidence is still ambiguous because it has raised fundamental questions that require more proof to be answered. The most important questions are: How can two totally different cellular fates act through a similar pathway? What is the separating edge? What forces a cell to choose one of them (death or differentiation)? To address these issues, we will concentrate on three groups of molecules; caspases as the key players of apoptosis, protein kinases, and phosphatases as the major regulators of many cellular and biochemical processes. The evidence reveals a triangle of caspases, kinases, and phosphatases in which their communication leads to the fine-tuning of caspases and consequently they determine cell fate.
细胞分化是多细胞生物生命过程中的关键之一。在这个现象中,一个非特化的细胞被转化为具有自身特定功能和形态的特化细胞。特化的一个要求是同时关闭涉及细胞增殖的途径,同时开启涉及分化的分子机制。与其他生物现象类似,细胞状态从增殖到分化的改变需要分子开关来响应内部或外部诱导物的变化。这些分子开关的本质尚未确定。然而,越来越多的证据表明,参与细胞凋亡的相同因子对分化过程有广泛的贡献。据我们所知,这一证据仍然存在争议,因为它提出了一些基本问题,需要更多的证据来回答。最重要的问题是:两种完全不同的细胞命运如何通过相似的途径发挥作用?区别在哪里?是什么迫使细胞选择其中一种命运(死亡或分化)?为了解决这些问题,我们将集中讨论三组分子;caspases 作为细胞凋亡的关键因子,蛋白激酶和磷酸酶作为许多细胞和生化过程的主要调节剂。证据揭示了 caspase、激酶和磷酸酶的三角形关系,它们之间的通讯导致 caspase 的精细调节,从而决定细胞命运。