The role of c-Jun N-terminal kinase (JNK)

• Main Authors: Yushin Chan, 詹育欣
• Other Authors: WHANG T.H.
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/60142941903169660454

碩士 === 長庚大學 === 基礎醫學研究所 === 92 === Paclitaxel is one of the microtubule-active agents. It interacts with β-tubulin, stabilzes the microtubule structure and thus alters the microtubule dynamics, resulting in the G2/M phase arrest. After a prolonged G2/M arrest, cells undergo apoptosis. Paclitaxel also activates JNK/SAPK (c-Jun N-terminal kinases/stress-activated protein kinases) and the activated JNK further phosphorylates c-Jun, a transcription factor, regulating downstream genes expression. JNK activation is required for the early phase of paclitaxel-induced apoptosis. However, the exact role of JNK in paclitaxel-induced apoptosis is not completely clear, and genes that are involved in paclitaxel-induced apoptosis remain to be clarified. SP600125, a JNK inhibitor, can inhibit the phosphorylation of c-Jun by JNK. Although the cytotoxicity of SP600125 was low, we found that, at high concentration of SP600125, cells arrest at the G2/M phase. Pretreatment of SP600125 inhibited the activation of c-Jun and reduced the paclitaxel-induced apoptosis. Using cDNA microarrays, I also analyzed the downstream target genes of c-Jun upon JNK activation. Twenty genes were selected and 14 among them were upregulated by paclitaxel and could be downregulated by SP600125; and the other 6 were downregulated by paclitaxel and could be upregulated by SP600125. Most of the genes were involved in the regulation of cytoskeleton, cell growth, apoptosis and other signal transduction pathways. Results of my study have detected some interesting genes that are worth further studies to characterize their roles in paclitaxel-induced apoptosis.