| First Author | Xu Y | Year | 2007 |
| Journal | Cell Death Differ | Volume | 14 |
| Issue | 1 | Pages | 79-91 |
| PubMed ID | 16645641 | Mgi Jnum | J:132255 |
| Mgi Id | MGI:3775569 | Doi | 10.1038/sj.cdd.4401928 |
| Citation | Xu Y, et al. (2007) Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3beta expression. Cell Death Differ 14(1):79-91 |
| abstractText | Amyloid precursor protein (APP) is a member of a gene family that includes two APP-like proteins, APLP1 and 2. Recently, it has been reported that APLP1 and 2 undergo presenilin-dependent gamma-secretase cleavage, as does APP, resulting in the release of an approximately 6 kDa intracellular C-terminal domain (ICD), which can translocate into the nucleus. In this study, we demonstrate that the APLP2-ICDs interact with CP2/LSF/LBP1 (CP2) transcription factor in the nucleus and induce the expression of glycogen synthase kinase 3beta (GSK-3beta), which has broad-ranged substrates such as tau- and beta-catenin. The significance of this finding is substantiated by the in vivo evidence of the increase in the immunoreactivities for the nuclear C-terminal fragments of APLP2, and for GSK-3beta in the AD patients' brain. Taken together, these results suggest that APLP2-ICDs contribute to the AD pathogenesis, by inducing GSK-3beta expression through the interaction with CP2 transcription factor in the nucleus. |
