The ubiquitin–proteasome system is inhibited by p53 protein expression in human ovarian cancer cells

Abstract The ubiquitin–proteasome system (UPS) and autophagy provide major cellular pathways for protein degradation. Since the p53 pathway controls autophagy, we investigated whether p53 regulates UPS in ovarian tumour cell lines. A reporter cell line (SKOV3-EGFPu) was established to measure UPS fu...

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Bibliographic Details
Published in:Cancer letters 2010-08, Vol.294 (1), p.82-90
Main Authors: Hwang, In Young, Baguley, Bruce C, Ching, Lai-Ming, Gilchrist, Catherine A
Format: Article
Language:English
Subjects:
Autophagy
Autophagy - drug effects
Cell Line, Tumor
Cloning, Molecular
Deoxyribonucleic acid
DNA
DNA Primers
EGFPu
Female
Gene Expression Regulation, Neoplastic
Genes, p53
Genes, Reporter
Hematology, Oncology and Palliative Medicine
Homeostasis
Humans
Membranes
Mutagenesis
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
p53
Plasmids
Proteasome activity
Proteasome Endopeptidase Complex - drug effects
Proteasome Endopeptidase Complex - genetics
Proteasome Endopeptidase Complex - metabolism
Proteasome Inhibitors
Proteins
Tumor Suppressor Protein p53 - drug effects
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Ubiquitin - antagonists & inhibitors
Ubiquitin - drug effects
Ubiquitin - genetics
Ubiquitin - metabolism
Up-Regulation
UPS function
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Summary:Abstract The ubiquitin–proteasome system (UPS) and autophagy provide major cellular pathways for protein degradation. Since the p53 pathway controls autophagy, we investigated whether p53 regulates UPS in ovarian tumour cell lines. A reporter cell line (SKOV3-EGFPu) was established to measure UPS function against a constant genetic background. Transient expression of either wild type or mutant p53 in SKOV3-EGFPu cells reduced UPS activity as compared to vector control. These results, together with those from endogenous p53 expression in seven ovarian cancer cell lines, suggest that expression of both wild-type and mutant p53 protein impairs UPS function. Thus, p53 expression may regulate protein homeostasis by down-regulating UPS function in response to cellular stress.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2010.01.025