RAD23 PHOSPHORYLATION IN DNA REPAIR AND PROTEASOME INTER

我们一直在研究泛素/蛋白酶体途径的底物识别机制。 我们以前确定的酵母G-α蛋白作为目标的N-末端规则途径，一个特定的底物靶向机制的泛素系统。G-α是对酵母的交配反应的调节剂，并且在功能上与其哺乳动物对应物相似。 我们最近发表了一篇论文，描述了G-α降解信号的分离和详细表征。N-末端规则途径的过度表达导致酵母细胞中的生长停滞。 我们分离出Rad 23作为这种毒性的抑制剂。Rad 23先前被鉴定为酵母和人类中核苷酸切除修复所需的因子。 我们最近报道，酵母和人类Rad 23 3蛋白可以形成稳定的相互作用与催化活性的蛋白酶体。目前的实验旨在确定介导Rad 23/蛋白酶体相互作用的序列和条件。 我们还在研究磷酸化在rad 23功能中的意义。 这些研究形成了我们实验室的一个主要新方向。

We have been studying the mechanism of substrate recognition by the ubiquitin/proteasome pathway. We previously identified the yeast G-alpha protein as a target of the N-end rule pathway; a specific substrate-targeting mechanism of the ubiquitin system. G-alpha is a regulator of the mating response to yeast, and is functionally similar to its mammalian counterparts. We recently published a paper describing the isolation and detailed characterization of a degradation signal to G-alpha. Overexpression of the N-end rule pathway causes growth arrest in yeast cells. We isolated Rad23 as a suppressor of this toxicity. Rad23 was previously identified as a factor that is required for nucleotide excision repair in yeast and humans. We have recently reported that both yeast and human Rad23 3 proteins can form stable interactions with catalytically active proteasomes. Current experiments are designed to determine the sequences and conditions that mediate Rad23/proteasome interaction. We are also investigating the significance of phosphorylation in rad23 function. These studies form a major new direction in our laboratory.