Cell Cycle Regulation, Protein Ubiquitination and Plant Development

细胞周期调控、蛋白质泛素化和植物发育

• 批准号: RGPIN-2018-05834
• 负责人: Wang, Hong
• 金额: $ 4.81万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744108
• 关键词: Cell; Cycle; Regulation; Protein; Ubiquitination

Cell division is one of the most fundamental processes underlying plant growth and development. Further, most cells produced from cell divisions by meristematic cells will eventually differentiate into other cell types. The long-term objectives of my research are: to gain fundamental knowledge on the key mechanisms regulating plant cell proliferation and differentiation, to understand how the cell cycle is linked to other biological processes in plants, and to use the new knowledge for practical applications. The cell division cycle in eukaryotes is regulated by cyclin-dependent kinases (CDKs), which can be regulated by several different mechanisms. Previously, we identified a family of plant-specific CDK inhibitors called ICKs (interactor/inhibitor of CDK) or KRPs (Kip-related proteins). For the last two decades our research has provided important understanding on these plant cell cycle regulators. The proposed research will determine how the levels of ICK proteins are regulated, and how ICKs may respond to various conditions serving to integrate environmental signals.Many proteins in eukaryotic species are regulated by protein ubiquitination, which involves a cascade of three biochemical reactions, catalyzed by three enzymes named as E1, E2 and E3 respectively. In the process, different polyubiquitin chains can be linked through different lysine (K) residues of ubiquitin. Previously, we identified the first plant E2 enzymes responsible for catalyzing K63-linked and K11-linked protein ubiquitination. The proposed research will further determine the molecular properties and regulation of UBC22 for K11-linked ubiquitination.ICKs and UBC22 have important roles in plant sexual development. In most plants, the female gametophyte development starts when one subepidermal cell in a young ovule differentiates into a megaspore mother cell (MMC). The MMC then produces four megaspores, one of which survives and becomes the functional megaspore (FM). Our recent results indicate that multiple ICK/KRPs function redundantly in normal plants to ensure the development of one embryo sac and thus one embryo per ovule. Further, when UBC22 is inactivated, the FM could not form normally in most ovules. The proposed work will investigate further how ICKs and UBC22 function in sexual plant reproduction. The proposed research is significant for a number of reasons. (a) It will provide new insight on a family of important cell cycle regulators, the newly identified UBC22 and Lys11-linked protein ubiquitination in plants. (b) The two lines of fundamental research have converged in plant sexual reproductive development. The knowledge generated could be useful for enhancing seed production and control of embryo development. (c) The two fundamental areas of plant biology along with diverse approaches and techniques to be used will provide excellent opportunities to train highly qualified personnel.

细胞分裂是植物生长发育的最基本过程之一。此外，由分生组织细胞分裂产生的大多数细胞最终将分化成其他细胞类型。我研究的长期目标是：获得调节植物细胞增殖和分化的关键机制的基础知识，了解细胞周期如何与植物中的其他生物过程联系在一起，并将新知识用于实际应用。细胞周期蛋白依赖性激酶（cyclin-dependent kinases，CDKs）是调节真核生物细胞分裂周期的重要因子，其调控机制有多种。以前，我们确定了一个植物特异性CDK抑制剂家族，称为ICK（CDK的相互作用物/抑制剂）或KRP（Kip相关蛋白）。 在过去的二十年里，我们的研究提供了重要的了解这些植物细胞周期调节剂。真核生物中的许多蛋白质都是通过蛋白质泛素化来调节的，这涉及到三个生化反应的级联反应，分别由三种酶E1，E2和E3催化。在该过程中，不同的聚泛素链可以通过泛素的不同赖氨酸（K）残基连接。在此之前，我们确定了第一个植物E2酶负责催化K63连接和K11连接的蛋白泛素化。ICKs和UBC 22在植物性发育中具有重要作用。在大多数植物中，雌配子体的发育始于胚珠中的一个亚表皮细胞分化为大孢子母细胞（MMC）。MMC然后产生四个大孢子，其中一个存活并成为功能大孢子（FM）。我们最近的研究结果表明，多个ICK/KRP冗余功能在正常植物中，以确保一个胚囊的发展，从而每个胚珠一个胚胎。此外，当UBC 22失活时，FM不能在大多数胚珠中正常形成。这项工作将进一步研究ICKs和UBC 22在植物有性生殖中的作用。拟议的研究是重要的，原因有几个。(a)它将提供一个重要的细胞周期调控家族的新见解，新发现的UBC 22和Lys 11连接的蛋白质在植物中的泛素化。(b)这两条基础研究路线在植物有性生殖发育方面已经汇合。所产生的知识可能有助于提高种子生产和控制胚胎发育。(c)植物生物学的这两个基本领域沿着各种方法和技术将为培养高素质人才提供极好的机会。