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Updated: Jul 16, 2026
09:08
Mapping Genome-wide Accessible Chromatin in Primary Human T Lymphocytes by ATAC-Seq
Published on: November 13, 2017
Specific sequence elements are required for the expression of functional tumor necrosis factor-alpha-converting
M E Milla1, M A Leesnitzer, M L Moss
1Department of Biochemistry, Johnson Research Foundation, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. mmilla@mail.med.upen.edu
The Journal of Biological Chemistry
|October 16, 1999
Summary
The pro domain of tumor necrosis factor-alpha-converting enzyme (TACE) inhibits its activity, but is required for secretion. Removing inhibitory domains allows for efficient secretion of active TACE.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Tumor necrosis factor-alpha-converting enzyme (TACE) is a zinc metalloprotease essential for releasing active tumor necrosis factor-alpha.
- Understanding TACE processing and secretion is crucial for developing therapeutic strategies targeting inflammatory diseases.
Purpose of the Study:
- To investigate the role of different TACE domains in its expression, secretion, and activation in insect cells.
- To elucidate the inhibitory function of the pro domain and the role of the cysteine-rich domain in TACE maturation.
Main Methods:
- Construction and overexpression of full-length and truncated human TACE variants in insect cells.
- Analysis of TACE expression, secretion, and activity using biochemical assays.
- Investigating the effect of domain deletions on TACE processing and stability.
Main Results:
- Full-length TACE is expressed inefficiently, with limited conversion to its active form in insect cells.
- Deletion of cytoplasmic and transmembrane domains enhances secretion of mature, active TACE.
- The pro domain acts as an inhibitor of the catalytic domain, and the cysteine-rich domain is involved in pro-domain release.
- The pro domain is essential for the secretion and intracellular stability of functional TACE.
Conclusions:
- The pro domain of TACE is a crucial inhibitor that also facilitates the secretion of the enzyme.
- The cysteine-rich domain plays a role in releasing the inhibitory pro domain, enabling TACE activation.
- Targeting TACE processing and secretion pathways could offer new therapeutic avenues.
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