| Summary: | 碩士 === 國立臺灣大學 === 微生物學研究所 === 107 === Protein aggregation can be found in a variety of diseases such as Parkinson’s and Alzheimer’s diseases. Many stresses at the molecular and cellular levels have been identified to provoke aging and play an important role in neurodegenerative diseases. Upon these stresses induce DNA damage response, ATM and ATR, two central regulators phosphorylate the downstream substrates to transduce signal. From the previous study, we found that the dephosphorylation of a co-chaperone facilitates protein folding under stresses. We speculate that the phosphorylation of chaperones/co-chaperones by stress/aging-induced ATM/ATR may also control the protein folding in neurodegenerative diseases. From the previous large-scale proteomic analysis of proteins phosphorylated by ATM/ATR in response to DNA damage, we found that 11 chaperones/co-chaperones phosphorylated. In my screening, the phosphorylation of DNAJA3 and DNAJB11 might be crucial for protein aggregations. Both DNAJA3 and DNAJB11 facilitate ErbB-2 degradation. DNAJA3 S169D and S169A, the mimetic phosphorylation and dephosphorylation mutations, reduced ErbB-2 than DNAJA3 mutations. However, DNAJB11 T188E, the mimetic phosphorylation, reduced ErbB-2 to a greater extent than DNAJB11 and DNAJB11 T188A.
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