Compensatory increase in USP14 activity accompanies impaired proteasomal proteolysis during aging
Subramaniam Ponnappan1, Michela Palmieri, Dennis H Sullivan
1Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. sponnappan@uams.edu
Mechanisms of Ageing and Development
|January 8, 2013
Summary
Aging impairs proteasomal proteolysis in T cells, but increased deubiquitinating enzyme USP14 activity is not the cause. USP14 and proteasome function are reciprocally regulated, maintaining ubiquitin homeostasis.
Area of Science:
- Cellular biology
- Immunology
- Biochemistry
Background:
- The deubiquitinating enzyme USP14 is crucial for proteasome function and ubiquitin homeostasis.
- Aging leads to reduced proteasomal proteolysis in human T lymphocytes.
Purpose of the Study:
- To investigate the role of USP14 in age-related decline of proteasomal proteolysis in T cells.
- To explore the relationship between USP14 activity and proteasome function during aging.
Main Methods:
- Assessed USP14 enzymatic activity in T cells from young and elderly donors.
- Utilized proteasome inhibitor lactacystin and USP14 inhibitor IU1.
- Measured IκBα degradation as an indicator of proteasomal proteolysis.
Main Results:
- USP14 activity was significantly higher in T cells from elderly donors.
- Increased USP14 activity was mimicked by proteasome inhibition.
- USP14 inhibition did not restore proteasomal proteolysis in elderly T cells.
Conclusions:
- Age-related decline in proteasomal proteolysis is independent of elevated USP14 activity.
- Reciprocal regulation between USP14 and proteasome catalytic activity is vital for cellular ubiquitin homeostasis.
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