Ubiquitin-mediated events in cell fate decisions

细胞在分裂时所做的最关键的决定是，是继续下去，尽快再次分裂（产生更多的细胞），还是暂时不分裂。这种决定细胞命运的错误会导致癌症和其他细胞增殖疾病。我们的总体目标是了解控制人类细胞分裂周期的途径的分子调控。在细胞分裂期间和之后，这些途径对于产生具有正确染色体数目、正确细胞结构和正确控制未来分裂决定的子细胞至关重要。我们已经开发了一些技术，使我们能够通过一种被称为泛素化的过程来探测涉及细胞成分修饰的关键事件。我们的初步研究表明，许多泛素介导的途径控制细胞分裂后立即发生的事件，并可能影响或决定再次分裂的决定。我们建议研究致力于两种可选择的细胞命运的细胞成分的泛素化。这可以让我们更好地了解癌症。目前针对分裂细胞的癌症治疗无法区分正在分裂的癌细胞和正在分裂的健康细胞，后者仍能控制自己的细胞命运。因此，区分具有不同命运的分裂细胞的能力将导致未来治疗的更好靶向性。

The most critical decision that a cell takes when it divides is whether to go ahead and divide again as soon as possible (making more cells), or not to divide for now. Errors in making this decision of cell fate cause cancer and other diseases of cell proliferation.Our general objective is to understand the molecular regulation of pathways that control the cell division cycle in human cells. These pathways are essential, during and after cell division, to generate daughter cells with correct chromosome numbers, correct cell architecture and correct control of future division decisions. We have developed techniques that allow us to probe critical events that involve modification of cellular components through a process known as ubiquitination. Our pilot study has shown that many ubiquitin-mediated pathways control events immediately following cell division and are likely to influence or determine the decision to divide again.We propose research that studies ubiquitination of cellular components in cells committed to the two alternative cell fates. This can provide us with a better understanding of cancer. Current cancer treatments that target dividing cells do not distinguish between dividing cancer cells and dividing healthy cells that retain control over their cell fate. Therefore the ability to distinguish dividing cells with different fates would lead to better targeting of future therapies.