Nuclear Import and Export Signals in Control of mouse alpha Actinin 2

• Main Authors: Kun-Mu, Lu, 呂昆穆
• Other Authors: Shih-Ming Huang
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/95985176939011493706

碩士 === 國防醫學院 === 生物化學研究所 === 95 === Mouse alpha actinin 2 (mACTN2) belongs to the spectrin proterin superfamily including spectrin, dystrophin and fimbrin (plastin) due to the similarity of their actin-binding domains. Our previous study suggested that mACTN2 can served as a coactivator for androgen receptor, estrogen receptor and thyroid receptor activities. ACTN2 primarily binds to the C-terminal region of GRIP1 (glucocorticoid receptor interacting protein 1) and AR, and then enhances the nuclear receptor functions. Previous studies have demonstrated that proteins that undergo nuclear import or export generally contain an nuclear localization signal (NLS) or nuclear export signal (NES), respectively. In this study, we further identified NLS and NES of mACTN2 and demonstrated that at least three NLS (codon 281-300, 371-400 and 701-894) and two leucine-rich NES (codons 66-78 and 510-521) regulating mACTN2 nucleocytoplasmic transportation. Any identified NES in mACTN2 was sufficient to direct nuclear exporting. Further studies demonstrate the nuclear exporting mechanism of mACTN2 was sensitive to a CRM1-dependent nuclear export inhibitor, leptomycin B. In addition, our data also suggested that the cytoplasmic subcellulation was correlated with the protein stability. In conclusion, the NES of mACTN2 was functional and that the nuclear export of mACTN2 might follow the CRM1-mediated export pathway and the degradation of mACTN2 was follow the proteasome-dependent pathway and occur in cytoplasm.