Human bleomycin hydrolase regulates the secretion of amyloid precursor protein

@article{Lefterov2000HumanBH,
  title={Human bleomycin hydrolase regulates the secretion of amyloid precursor protein},
  author={Iliya Lefterov and Radosveta Koldamova and John S. Lazo},
  journal={The FASEB Journal},
  year={2000},
  volume={14},
  pages={1837 - 1847}
}
Human bleomycin hydrolase (hBH) is a neutral cysteine protease genetically associated with increased risk for Alzheimer disease. We show here that ectopic expression of hBH in 293APPwt and CHOAPPsw cells altered the processing of amyloid precursor protein (APP) and increased significantly the release of its proteolytic fragment, β amyloid (Aβ). We also found that hBH interacted and colocalized with APP as determined by subcellular fractionation, in vitro binding assay, and confocal… 
Cysteine 73 in bleomycin hydrolase is critical for amyloid precursor protein processing.
TLDR
A critical role for cysteine 73 of hBH in mediating APP processing is indicated, which is a major constituent of the Alzheimer's disease-associated amyloid plaques.
Intracellular pathways of folded and misfolded amyloid precursor protein degradation.
  • J. Hare
  • Biology, Chemistry
    Archives of biochemistry and biophysics
  • 2006
Cysteine Proteases Bleomycin Hydrolase and Cathepsin Z Mediate N-terminal Proteolysis and Toxicity of Mutant Huntingtin*
TLDR
A genome-wide screen using an RNA-silencing approach and an assay for huntingtin proteolysis involving overexpression of individual proteases with huntingtin identified 11 enzymes, with two major candidates to carry out the cp-2 cleavage, bleomycin hydrolase and cathepsin Z, which are both cysteine proteases of a papain-like structure.
Effects of acetylate hyperforin on the processing of amyloid precursor protein.
TLDR
The findings suggest that ace-HF can modulate α-secretase-mediated APP processing via a PKC signaling pathway, and may be used to improve psychopathologic symptoms of Alzheimer's disease.
Bleomycin Hydrolase Is Regulated Biphasically in a Differentiation- and Cytokine-dependent Manner
TLDR
The results suggest that BH transcription would be modulated during both differentiation and inflammation, suggesting a defect of the filaggrin degradation pathway in AD.
Role of Lysyl Oxidase Propeptide in Secretion and Enzyme Activity
TLDR
This study points out the requirement of the LOX‐PP for pro‐LOX exit from the ER and is the first to highlight the influence of LOX•PP glycosylation on LOX enzyme activity.
Protective Mechanisms against Homocysteine Toxicity
TLDR
It is shown that Hcy-thiolactone is hydrolyzed by an intracellular enzyme, which is purified to homogeneity from human placenta and identified by proteomic analyses as human bleomycin hydrolase (hBLH).
Expression of bleomycin hydrolase in keratinization disorders
TLDR
In the present study, immunohistochemical studies of BH and other serine/cysteine proteases in human normal skin and lesional skin with keratinization disorders revealed that BH- and caspase-14-positive staining had higher intensity than those of the other protease in normal epidermis.
Analysis of the Role of Bleomycin Hydrolase in Antigen Presentation and the Generation of CD8 T Cell Responses1
TLDR
It is shown that BH-deficient cells from mice are unimpaired in their ability to present epitopes from N-extended precursors or whole Ags and express normal levels of MHC class I molecules, and BH does influence presentation of some Ags, although its role is largely redundant with other aminopeptidases.
...
...

References

SHOWING 1-10 OF 59 REFERENCES
A Novel Brain Cysteine Protease Forms an SDS Stable Complex with the β‐Amyloid Precursor Protein a
TLDR
The enzyme isolated from AD brain is capable of digesting APP and generating a short peptide recognizable by antibodies specific to the C‐terminus of APP, and Interestingly, the purified protease also forms heat‐ and SDS‐stable complexes with APP.
A novel brain cysteine protease forms an SDS stable complex with the beta-amyloid precursor protein.
TLDR
The enzyme isolated from AD brain is capable of digesting APP and generating a short peptide recognizable by antibodies specific to the C-terminus of APP, and Interestingly, the purified protease also forms heat- and SDS-stable complexes with APP.
Human bleomycin hydrolase binds ribosomal proteins.
TLDR
The data strongly suggest that hBH exists as both a free cytosolic and ribosome-associated protein.
Glycosylphosphatidylinositol-anchored Proteins Play an Important Role in the Biogenesis of the Alzheimer’s Amyloid β-Protein*
TLDR
Findings provide strong evidence that one or more GPI-anchored proteins play an important role in β-secretase activity and Aβ secretion in mammalian cells.
Amyloid β-peptide is produced by cultured cells during normal metabolism
TLDR
The unexpected identification of the 4K (Mr 4,000) Aβ and a truncated form of Aβ in media from cultures of primary cells and untransfected and β-APP-transfected cell lines grown under normal conditions provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A β, the primary protein constituent of the senile plaques of Alzheimer's disease.
Amyloid beta-peptide is produced by cultured cells during normal metabolism.
TLDR
The unexpected identification of the 4K (M(r) 4,000) A beta and a truncated form of A beta in media from cultures of primary cells and untransfected and beta-APP-transfected cell lines grown under normal conditions provides the basis for using simple cell culture systems to identify drugs that block the formation or release of ABeta.
Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells.
TLDR
It is shown that 3- and 4-kDa peptides derived from amyloid precursor protein are normally secreted and evidence that glial cells are a major source of beta-amyloid production in the brain is provided.
Detection of a Novel Intraneuronal Pool of Insoluble Amyloid β Protein that Accumulates with Time in Culture
TLDR
It is found that formic acid extraction of the NT2N cells solubilized a pool of previously undetectable Aβ that accounted for over half of the total intracellular Aβ, suggesting that Aβ amyloidogenesis may be initiated within living neurons rather than in the extracellular space.
Essential binding and functional domains of human bleomycin hydrolase.
Bleomycin hydrolase (BH) is unusual among cysteine proteinases because it appears to form multihomomeric structures, inactivates the antitumor glycopeptide bleomycin, and contains a unique C-terminal
...
...