Format

Send to

Choose Destination
Biochim Biophys Acta. 2007 Jun;1773(6):736-46. Epub 2007 Feb 14.

Notch1 intracellular domain suppresses APP intracellular domain-Tip60-Fe65 complex mediated signaling through physical interaction.

Author information

1
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Yongbong-dong, Buk-ku, Gwangju, 500-757, Republic of Korea.

Abstract

The amyloid beta-precursor protein (APP) and the Notch receptor are both type 1 integral transmembrane proteins, and both are cleaved by presenilin-dependent gamma-secretase activity. In this study, we have demonstrated that the Notch intracellular domain (Notch1-IC) suppresses APP-intracellular domain (AICD)-mediated ROS generation and cell death after being processed by gamma secretase. Notch1-IC physically interacts with AICD, Fe65, and Tip60, thereby disrupting the association of the AICD-Fe65-Tip60 trimeric transcription activator complex in AICD signaling. AICD-Fe65-Tip60 mediated reactive oxygen species generation was found to be suppressed by Notch1-IC. Furthermore, AICD-Fe65-Tip60 was shown to mediate cell death in human neuroblastoma cells, and the overexpression of Notch1-IC inhibited cell death induced by AICD-Fe65-Tip60. Collectively, our findings indicate that Notch1-IC plays the role of a negative regulator in AICD signaling via the disruption of the AICD-Fe65-Tip60 trimeric complex.

PMID:
17368826
DOI:
10.1016/j.bbamcr.2007.02.001
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center