A RIP tide in neuronal signal transduction.
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.
Ebinu
Julius O
JO
Department of Neurology, Harvard Medical School and, Division of Neuroscience, The Children's Hospital, Enders 260, 300 Longwood Avenue, 02115, Boston, MA 02115, USA.
Yankner
Bruce A
BA
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D009687:Nuclear Proteins; D010447:Peptide Hydrolases