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Compensatory increase in USP14 activity accompanies impaired proteasomal proteolysis during aging
- Source :
- Mechanisms of ageing and development. 134(1-2)
- Publication Year :
- 2012
-
Abstract
- The deubiquitinating enzyme, USP14, found in association with the proteasome is essential in mediating ubiquitin trimming and in ensuring ubiquitin-homeostasis. As aging is accompanied by a significant decline in proteasomal proteolysis in primary human T lymphocytes, we evaluated the contributory role of USP14 in this decline. Our studies for the first time demonstrate that enzymatic activity of proteasome-associated USP14 is significantly higher in T cells obtained from elderly donors. Additionally, such an increase in USP14 activity could be mimicked by chemically inhibiting the proteasome, using lactacystin. Thus, USP14 activity appears to be reciprocally regulated by the catalytic function of the 26S proteasome. To determine whether the inhibition of USP14 activity counter regulates proteasomal proteolysis, T cells pretreated with a small molecule inhibitor of USP14, IU1, were activated and assessed for IκBα degradation as a measure of proteasomal proteolysis. While T cells obtained from young donors demonstrated increased degradation of IκBα, those from the elderly remained unaffected by IU1 pretreatment. Taken together, these results demonstrate that the decrease in proteolysis of proteasomal substrates during aging is independent of the increased USP14 activity and that the reciprocal regulation of USP14 and proteasomal catalytic activity may be necessary to maintain cellular ubiquitin homeostasis.
- Subjects :
- Adult
Male
Aging
Proteasome Endopeptidase Complex
Proteolysis
T-Lymphocytes
Lactacystin
Biology
Cysteine Proteinase Inhibitors
Article
Deubiquitinating enzyme
chemistry.chemical_compound
Ubiquitin
NF-KappaB Inhibitor alpha
medicine
Humans
Aged
chemistry.chemical_classification
Aged, 80 and over
Hemostasis
medicine.diagnostic_test
Ubiquitin homeostasis
Cell biology
Acetylcysteine
IκBα
Enzyme
Biochemistry
Proteasome
chemistry
biology.protein
Female
I-kappa B Proteins
Ubiquitin Thiolesterase
Developmental Biology
Subjects
Details
- ISSN :
- 18726216
- Volume :
- 134
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Mechanisms of ageing and development
- Accession number :
- edsair.doi.dedup.....f31242124466912b5376bfa037d17c19