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Title: Expression of the fetal Alz-50 clone 1 protein induces apoptotic cell death

The fetal Alz-50 clone 1 (FAC1) protein exhibits altered expression patterns in neurodegenerative disease. Though it has been shown to bind DNA in a site-specific, phosphorylation-dependent manner, its cellular function remains unknown. Here, we demonstrate that overexpression of FAC1 in PT67 fibroblasts induces nuclear condensation and cleavage of caspase 3 to its active form indicating induction of apoptosis. The amino-terminal domain of FAC1 is necessary and sufficient to induce both nuclear condensation and activation of caspase 3. Disruption of FAC1 interaction with a known binding partner, kelch-like ECH-associated protein 1 (Keap1), enhances activation of caspase 3. Keap1 is known to block activation of the antioxidant response gene products by direct interaction with the transcriptional activator, Nrf2. Disruption of the Keap1:Nrf2 interaction enhances FAC1 induction of apoptosis. These findings suggest a role for FAC1 in apoptosis following release of Nrf2 from Keap1 in response to oxidative stress.
Authors:
 [1] ;  [1] ;  [2]
  1. Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104-6030 (United States)
  2. Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104-6030 (United States). E-mail: Jordan@path.dental.upenn.edu
Publication Date:
OSTI Identifier:
20713387
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 336; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2005.08.127; PII: S0006-291X(05)01823-1; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; APOPTOSIS; CLEAVAGE; DNA; ECR HEATING; FIBROBLASTS; GENES; NERVOUS SYSTEM DISEASES; PHOSPHORYLATION; PROTEINS; TRANSCRIPTION