FEBS Letters | |
Impas 1 possesses endoproteolytic activity against multipass membrane protein substrate cleaving the presenilin 1 holoprotein | |
Madera, Dmitri1  Grigorenko, Anastasia1  Rogaev, Evgeny I1  Moliaka, Yuri K1  | |
[1] University of Massachusetts Medical School, Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, 303 Belmont Street, Worcester, MA 01604, USA | |
关键词: Presenilins; Protease; Intramembrane proteolysis; Transmembrane precursor proteins; IMPAS; Alzheimer's disease; Expression; Mammalian cells; Ab; antibody; AD; Alzheimer's disease; APP; amyloid precursor protein; chr; chromosome; CTF; carboxy-terminal fragment; DMSO; dimethyl sulfoxide; HD; hydrophobic domain; HEK; human embryonic kidney; IMP; intramembrane protease-associated or intramembrane protease aspartic protein; IMPAS; family of these proteins; NTF; N-terminal fragment; PS; presenilin; SPP; signal peptide peptidase; wt; wild type; | |
DOI : 10.1016/S0014-5793(03)01489-3 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Presenilins (PS1 and PS2) are supposed to be unusual aspartic proteases and components of the γ-secretase complex regulating cleavage of type I proteins. Multiple mutations in PS1 are a major cause of familial early-onset Alzheimer's disease (AD). We and others recently identified PS-related families of proteins (IMPAS/PSH/signal peptide peptidases (SPP)). The functions of these proteins are yet to be determined. We found that intramembrane protease-associated or intramembrane protease aspartic protein Impas 1 (IMP1)/SPP induces intramembranous cleavage of PS1 holoprotein in cultured cells coexpressing these proteins. Mutations in evolutionary invariant sites in hIMP1 or specific γ-secretase inhibitors abolish the hIMP1-mediated endoproteolysis of PS1. In contrast, neither AD-like mutations in hIMP1 nor in PS1 substrate abridge the PS1 cleavage. The data suggest that IMP1 is a bi-aspartic polytopic protease capable of cleaving transmembrane precursor proteins. These data, to our knowledge, are a first observation that a multipass transmembrane protein or the integral protease per se may be a primary substrate for an intramembranous proteolysis.
【 授权许可】
Unknown
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