Cell Cycle Regulation, Protein Ubiquitination and Plant Development

细胞分裂是植物生长发育最基本的过程之一。此外，分生组织细胞分裂产生的大多数细胞最终会分化成其他类型的细胞。我研究的长期目标是：获得调控植物细胞增殖和分化的关键机制的基础知识，了解细胞周期是如何与植物中的其他生物过程联系在一起的，并将新知识用于实际应用。*真核生物的细胞分裂周期受细胞周期蛋白依赖性蛋白激酶(CDKs)的调控，CDKs可以通过几种不同的机制来调节。在此之前，我们发现了一类植物特异性的CDK抑制剂，称为ICKs(CDK的相互作用因子/抑制物)或krps(KIP相关蛋白)。在过去的二十年里，我们的研究为这些植物细胞周期调节因子提供了重要的理解。这项拟议的研究将确定ICK蛋白的水平是如何调节的，以及ICK可能如何对各种整合环境信号的条件做出反应。真核物种中的许多蛋白质都受到蛋白质泛素化的调控，这涉及三个生化反应的级联，分别由三种酶E1、E2和E3催化。在这个过程中，不同的多泛素链可以通过不同的泛素赖氨酸(K)残基连接起来。在此之前，我们鉴定了第一个负责催化K63和K11连接的蛋白质泛素化的植物E2酶。这项研究将进一步确定UBC22在K11连锁泛素化过程中的分子特性和调控。在大多数植物中，当幼小胚珠中的一个下胚珠细胞分化成大孢子母细胞时，雌配子体的发育就开始了。然后，MMC产生四个大孢子，其中一个存活下来，成为功能性大孢子(FM)。我们最近的研究结果表明，在正常植物中，多个ick/krp的功能是冗余的，以确保一个胚囊的发育，从而保证每个胚珠一个胚胎的发育。此外，当UBC22失活时，大多数胚珠中的FM不能正常形成。这项拟议的工作将进一步调查ICKS和UBC22如何在植物有性繁殖中发挥作用。*这项拟议的研究具有重要意义，原因有很多。(A)它将提供关于一系列重要的细胞周期调节因子的新见解，即新发现的植物中与UBC22和Lys11相关的蛋白质泛素化。(B)在植物有性生殖发育方面，这两个基础研究方向已经汇合。所产生的知识可能有助于提高种子产量和控制胚胎发育。(C)植物生物学的两个基本领域以及将采用的不同方法和技术将为培训高素质人员提供极好的机会。

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.