Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 336, Issue 2, Pages 490-495Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2005.08.127
Keywords
transcription; programmed cell death; caspase 3; neurodegeneration
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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 (Keapl), enhances activation of caspase 3. Keapl is known to block activation of the antioxidant response gene products by direct interaction with the transcriptional activator, Nrf2. Disruption of the Keapl:Nrf2 interaction enhances FAC1 induction of apoptosis. These findings suggest a role for FAC1 in apoptosis following release of Nrf2 from Keapl in response to oxidative stress. (c) 2005 Elsevier Inc. All rights reserved.
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