The ubiquitin-proteasome system is inhibited by p53 protein expression in human ovarian cancer cells.
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.
Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand.
In Young
IY
Hwang
Bruce C
BC
Baguley
Lai-Ming
LM
Ching
Catherine A
CA
Gilchrist
D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016158:Genes, p53; D006706:Homeostasis; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010957:Plasmids; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D017931:DNA Primers; D061988:Proteasome Inhibitors; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex