Guay-Woodford Lisa M
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Clin Invest. 2004 Nov;114(10):1404-6. doi: 10.1172/JCI23544.
Polycystin-1, the protein encoded by the principal gene involved in autosomal dominant polycystic kidney disease, has been implicated in extracellular sensing as well as in cell-cell and cell-matrix interactions. However, the precise mechanisms involved in polycystin-1 signaling are not well defined. A report in this issue of the JCI demonstrates that the C-terminal tail of polycystin-1 is cleaved from the membrane through regulated intramembrane proteolysis (RIP) and that this domain translocates to the nucleus, where it activates the AP-1 transcription pathway. This translocation appears to be modulated by polycystin-2, with which polycystin-1 is thought to interact. These findings provide what we believe to be the first evidence that polycystin-1 can signal directly to the nucleus and that polycystin-1-polycystin-2 interactions do not require colocalization of these proteins in the same membrane compartment.
多囊蛋白-1是常染色体显性多囊肾病相关主要基因编码的蛋白质，它参与细胞外传感以及细胞间和细胞与基质的相互作用。然而，多囊蛋白-1信号传导的确切机制尚不清楚。本期《临床研究杂志》的一篇报道表明，多囊蛋白-1的C末端尾巴通过调节性膜内蛋白水解（RIP）从膜上裂解下来，并且该结构域转移到细胞核，在那里它激活AP-1转录途径。这种转移似乎受多囊蛋白-2调节，人们认为多囊蛋白-1与多囊蛋白-2相互作用。这些发现提供了我们认为的首个证据，即多囊蛋白-1可以直接向细胞核发出信号，并且多囊蛋白-1与多囊蛋白-2的相互作用并不要求这些蛋白质在同一膜区室中共定位。
