Related Experiment Video
Updated: Jul 12, 2026
10:05
Hydrogel Nanoparticle Harvesting of Plasma or Urine for Detecting Low Abundance Proteins
Published on: August 8, 2014
Plasma hyaluronan-binding protein is a serine protease
1Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook, Stony Brook, New York 11794-8101, USA.
The Journal of Biological Chemistry
|May 19, 2000
Summary
A novel protease in serum cleaves CTCF, a key transcription factor for amyloid precursor protein. This protease, identified as plasma hyaluronan-binding protein, is inhibited by amyloid precursor protein itself.
Area of Science:
- Molecular Biology
- Protein Biochemistry
- Gene Regulation
Background:
- The transcription factor CTCF (CCCTC-binding factor) is crucial for regulating gene expression, including that of the amyloid beta-protein precursor (APP) gene.
- Serum contains proteolytic activities that can modify proteins, potentially impacting cellular functions.
Purpose of the Study:
- To identify and characterize the serum protease that cleaves CTCF.
- To investigate the functional implications of CTCF cleavage on its DNA-binding ability and its role in APP gene transcription.
Main Methods:
- Purification of the serum protease responsible for CTCF cleavage using biochemical techniques.
- Partial sequencing and identification of the purified protease.
- Analysis of protease activity using serine protease inhibitors and beta-mercaptoethanol reduction.
- Localization of the protease's active domain using radiolabeling.
Main Results:
- A serum protease was purified and identified as plasma hyaluronan-binding protein (PHBP).
- PHBP cleaves CTCF at three sites, altering its mobility shift pattern while retaining DNA-binding capacity.
- The protease activity is inhibited by serine protease inhibitors, including a domain within the amyloid beta-protein precursor.
- PHBP is a 70-kDa protein composed of 44-kDa and 30-kDa subunits, with the serine protease domain located on the 30-kDa subunit.
Conclusions:
- Plasma hyaluronan-binding protein is a serum protease that modifies CTCF, a key regulator of the amyloid beta-protein precursor promoter.
- The cleavage of CTCF by PHBP may represent a regulatory mechanism influencing APP gene transcription.
- The interaction between PHBP and the amyloid beta-protein precursor inhibitor domain suggests a complex regulatory network.
Related Concept Videos
01:09Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
01:05Proteoglycans
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
01:23Glycosaminoglycans
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
01:21Matrix Proteoglycans and Glycoproteins
Proteoglycans are extensively glycosylated proteins, commonly found in the extracellular matrix, interwoven with collagen fibers. Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers associated with large amounts of proteoglycans. These proteoglycans have long negative charges that attract cations, which in turn attract water molecules. This influx of ions and water molecules swells up the proteoglycan like a water-soaked gel that can...
01:29Drug Distribution: Plasma Protein Binding
Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
01:30Drug Binding to Blood Components
When drugs enter systemic circulation, they interact with various components of the blood, including proteins such as human serum albumin (HSA), α1-acid glycoprotein (AAG), lipoproteins, globulins, and red blood cells (RBCs).
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are further...
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are further...