| First Author | Guo Q | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 6 | Pages | 4596-603 |
| PubMed ID | 14627703 | Mgi Jnum | J:87963 |
| Mgi Id | MGI:3028747 | Doi | 10.1074/jbc.M309811200 |
| Citation | Guo Q, et al. (2004) AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4. J Biol Chem 279(6):4596-603 |
| abstractText | Aggregation of the neurotoxic amyloid beta peptide 1-42 (Abeta-(1-42)) in the brain is considered to be an early event in the pathogenesis of Alzheimer's disease (AD). Par-4 (prostate apoptosis response-4) is a leucine zipper protein that is pro-apoptotic and associated with neuronal degeneration in AD. Overexpression of Par-4 significantly increased production of Abeta-(1-42) after initiation of apoptotic cascades, indicating factors regulating apoptotic pathways may also affect processing of beta-amyloid precursor protein (APP). AATF (apoptosis-antagonizing transcription factor) was recently identified as an interaction partner of DAP-like kinase (Dlk), a member of the DAP (death-associated protein) kinase family. AATF antagonizes apoptosis induced by Par-4, suggesting that AATF might directly or indirectly participate in regulation of Par-4 activity. We now report that AATF colocalizes with Par-4 in both cytoplasmic and nuclear compartments, and it interacts directly and selectively with Par-4 via the leucine zipper domain in neural cells. Par-4 induced an aberrant production and secretion of Abeta in neuroblastoma IMR-32 cells after apoptotic cascades are initiated. Co-expression of AATF completely blocked aberrant production and secretion of Abeta-(1-42) induced by Par-4, and AATF/Par-4 complex formation was essential for the inhibitory effect of AATF on aberrant Abeta secretion. These results indicate that AATF is an endogenous antagonist of Par-4 activity and an effective inhibitor of aberrant Abeta production and secretion under apoptotic conditions. |
