RAD23 PHOSPHORYLATION IN DNA REPAIR AND PROTEASOME INTER

我们一直在研究泛素/蛋白酶体途径识别底物的机制。我们之前发现酵母g - α蛋白是n端规则通路的靶标；泛素系统的特异性底物靶向机制。g - α是酵母交配反应的调节因子，其功能与哺乳动物相似。我们最近发表了一篇论文，描述了g - α退化信号的分离和详细表征。n端规则通路的过度表达导致酵母细胞生长停滞。我们分离出Rad23作为这种毒性的抑制因子。Rad23先前被确定为酵母和人类核苷酸切除修复所需的因子。我们最近报道了酵母和人Rad23蛋白都能与催化活性蛋白酶体形成稳定的相互作用。目前的实验旨在确定介导Rad23/蛋白酶体相互作用的序列和条件。我们也在研究磷酸化在rad23功能中的意义。这些研究构成了我们实验室一个重要的新方向。

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.