Disease relevance of BPTF

• The fetal Alz-50 reactive clone 1 (FAC1) protein exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease [1].
• Phosphatase treatment of neuroblastoma nuclear extracts reduces FAC1 DNA binding affinity [2].
• In this study we report the localization and expression of FAC1 protein in developing, normal adult and amyotrophic lateral sclerosis (ALS) lumbar spinal cord [3].

Psychiatry related information on BPTF

• Numerous FAC1 immunoreactive swollen dendrites were also present in the hippocampus of Alzheimer's disease and dementia with Lewy bodies patients [4].

High impact information on BPTF

• In NIH3T3 cells, luciferase reporter plasmids containing the identified binding site (CACAACAC) were repressed by cotransfected FAC1 whether the binding site was proximal or distal to the transcription initiation site [5].
• Nuclear extracts from neural and non-neural cell lines contained a DNA-binding activity with similar specificity and nucleotide requirements as the recombinant FAC1 protein [5].
• This DNA-binding activity can be attributed to FAC1 since it is dependent upon the presence of FAC1 and behaves identically on a nondenaturing polyacrylamide gel as transiently transfected FAC1 [5].
• Using the polymerase chain reaction-assisted binding site selection assay, we have identified a DNA sequence recognized by recombinant FAC1 [5].
• The FAC1 amino acid sequence contains regional homology to transcriptional regulators [5].

Biological context of BPTF

• By immunoblot analysis, FAC1 and ZF87/MAZ exhibit similar tissue distribution and co-localize to pathologic structures in Alzheimer's disease brain [6].
• FAC1, on the other hand, recognizes a conformational interface that includes the proline/alanine-rich domain of ZF87/MAZ and the first zinc finger [6].
• Disruption of the Keap1:Nrf2 interaction enhances FAC1 induction of apoptosis [7].
• These findings suggest a role for FAC1 in apoptosis following release of Nrf2 from Keap1 in response to oxidative stress [7].
• Mutation of any 2 adjacent base pairs in the identified binding site dramatically reduced the binding preference of FAC1, demonstrating that the binding is specific for the identified site [5].

Anatomical context of BPTF

• 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 [7].
• Our studies demonstrate that NGF induces a rapid, transient increase in FACI mRNA that is dependent upon ERK activation, and that FAC1 protein exhibits altered subcellular distribution during neurite outgrowth [8].
• FAC1 exhibited a rapid redistribution from the cytoplasm to the perinuclear region in PC12 cells treated with Abeta [9].
• By immunocytochemistry, the FAC1 protein is almost exclusively localized in the nucleus of neurons in the adult neocortex [10].
• FAC1 protein is also immunolocalized in swollen dendrites of hippocampal pyramidal cells observed in some cases of early stage AD [11].

Associations of BPTF with chemical compounds

• DEM does not affect the ability of FAC1 to bind hKeap1 in our assay [1].
• Finally, inhibition of cellular serine/threonine phosphatases results in increased FAC1 DNA binding activity [2].

Other interactions of BPTF

• Coexpression of FAC1 and ZF87/MAZ suggest that interaction of these two proteins will have biological implications for gene regulation in neurodegeneration [6].
• Disruption of FAC1 interaction with a known binding partner, kelch-like ECH-associated protein 1 (Keap1), enhances activation of caspase 3 [7].

Analytical, diagnostic and therapeutic context of BPTF

• Assignment of the human FAC1 gene to chromosome 17q24 by fluorescence in situ hybridization [12].
• Confocal laser microscopy demonstrated the presence of actin in FAC1 labelled Hirano bodies, and ultrastructural analysis confirmed the presence of a lattice structure within FAC1 labelled Hirano bodies [4].
• There are three levels of care provided by ambulance personnel including a basic-level ambulance crew (First Aid Class One, FAC-1), a second level (Standard First Aid Class, SFAC), and the highest level (Emergency Life Saving Technician, ELST) [13].

References