Lee So-Youn, Kim Jung-Woong, Jeong Mi-Hee, An Joo-Hee, Jang Sang-Min, Song Ki-Hyun, Choi Kyung-Hee
Laboratory of Molecular Biology, Department of Life Science, College of Natural Sciences, Chung-Ang University, 221 Heuksuk-Dong, Dongjak-Ku, Seoul, Republic of Korea.
FEBS Lett. 2008 Aug 20;582(19):2826-32. doi: 10.1016/j.febslet.2008.07.021. Epub 2008 Jul 24.
The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses and can trigger apoptosis in many cell types, including neurons. In this study, we have shown that the Microtubule-Associated Protein 1B (MAP1B) light chain can interact with the tumor suppressor p53. We also demonstrate that both p53 and the MAP1B light chain (MAP1B-LC1) alter their localization from the cytoplasm to the nucleus when neuroblastoma cells, SH-SY5Y, are treated with doxorubicin. Additionally, we demonstrate that the MAP1B-LC1 negatively regulates p53-dependent transcriptional activity of a reporter construct driven by the p21 promoter. Consequently, MAP1B-LC1 binds to p53 and this interaction leads to the inhibition of doxorubicin-induced apoptosis in SH-SY5Y cells.
肿瘤抑制因子和转录因子p53是细胞应激反应的关键调节因子,可在包括神经元在内的多种细胞类型中触发凋亡。在本研究中,我们发现微管相关蛋白1B(MAP1B)轻链可与肿瘤抑制因子p53相互作用。我们还证明,当用阿霉素处理神经母细胞瘤细胞SH-SY5Y时,p53和MAP1B轻链(MAP1B-LC1)都会从细胞质转移至细胞核。此外,我们证明MAP1B-LC1负向调节由p21启动子驱动的报告基因构建体的p53依赖性转录活性。因此,MAP1B-LC1与p53结合,这种相互作用导致SH-SY5Y细胞中阿霉素诱导的凋亡受到抑制。