Ebinu Julius O, Yankner Bruce A
Department of Neurology, Harvard Medical School and, Division of Neuroscience, The Children's Hospital, Enders 260, 300 Longwood Avenue, 02115, Boston, MA 02115, USA.
Neuron. 2002 May 16;34(4):499-502. doi: 10.1016/s0896-6273(02)00704-3.
The generation of nuclear signaling proteins by regulated intramembrane proteolysis (RIP) is a new paradigm of signal transduction. Mammalian proteins that are processed by RIP include SREBP-1, Notch-1, amyloid precursor protein (APP), and ErbB-4. Intramembranous gamma-secretase cleavage of APP plays a central role in Alzheimer's disease by generating the amyloid beta protein. An intriguing possibility is that the cognate C-terminal fragment generated by gamma-secretase cleavage could also play a role through the regulation of nuclear signaling events. Thus, RIP may contribute to both brain development and degeneration and may provide unexpected diversity to the signaling repertoire of a cell.
通过调节性膜内蛋白水解（RIP）产生核信号蛋白是信号转导的一种新范式。经RIP加工的哺乳动物蛋白包括固醇调节元件结合蛋白-1（SREBP-1）、Notch-1、淀粉样前体蛋白（APP）和表皮生长因子受体4（ErbB-4）。APP的膜内γ-分泌酶切割通过产生β淀粉样蛋白在阿尔茨海默病中起核心作用。一个有趣的可能性是，γ-分泌酶切割产生的同源C末端片段也可能通过调节核信号事件发挥作用。因此，RIP可能对大脑发育和退化都有贡献，并可能为细胞的信号库提供意想不到的多样性。
