A RIP tide in neuronal signal transduction |
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Authors: | Ebinu Julius O Yankner Bruce A |
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Affiliation: | Department of Neurology, Harvard Medical School and, Division of Neuroscience, The Children's Hospital, Enders 260, 300 Longwood Avenue, 02115, Boston, MA 02115, USA. |
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Abstract: | 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. |
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