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.
Strachan
Gordon D
GD
Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104-6030, USA.
Ostrow
Liya Avshalumov
LA
Jordan-Sciutto
Kelly L
KL
D034961:Antigens, Nuclear; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
D034961:Antigens, Nuclear; D053148:Caspase 3; D020169:Caspases; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; D011506:Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C431364:KEAP1 protein, human; C495635:NFE2L2 protein, human; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins; C505407:CASP3 protein, human