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標題: 182位置酪胺酸的磷酸化降低Rad23蛋白與泛素的結合能力及其所參與的蛋白質降解途徑
Phosphorylation of Tyrosine-182 decreases the ubiquitin binding ability and Rad23-mediated protein degradation
作者: 陳柏蓉
關鍵字: Rad23;磷酸化;phosphorylation
出版社: 生物醫學研究所
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Rad23 is evolutionarily conserved for involving in DNA nuclear excision repair (NER) and ubiquitin-proteasome system (UPS) from yeast to human. However, the signaling regulation of Rad23 function is still unknown. To investigate the signaling control for Rad23 function, site-directed mutagenesis and in vitro kinase assay were used to prove Tyrosine-182, the highly conserved residue in UBA1 domain among species, is phosphotylated by Rad53. Y182F/D mutants didn't affect the stability of Rad23 itself. Functional analysis showed that Y182F/D mutants were similar to wild-type in UV sensitivity and Rad4 binding affinity. Interestingly, Y182D mutant significantly reduced the K48- and K63-linked polyubiquitin chain binding ability in vitro and in vivo and slightly decreased the association with 26S subunits. Ub-Pro-βgal, a substrate of the ubiquitin-fusion degradation pathway, was significantly stabilized in strains that over-expressed wild-type Rad23 and Rad23Y182F, but not Y182D mutant. Furthermore, the lower dimerization was observed in wild-type /Rad23Y182D and Rad23Y182D/ Rad23Y182D. Based on these results, we suggest that the ubiquitin chain binding ability of Rad23 might be down-regulated through the phosphorylation of Y182 on UBA1 domain, which consequently affect the Rad23-mediated proteolysis. However, the molecular mechanism for Y182 phosphorylation by signaling will be further investigated.
其他識別: U0005-2606200814313700
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