Cell survival from chemotherapy depends on NF-kappaB transcriptional up-regulation of coenzyme Q biosynthesis.
BACKGROUND
Coenzyme Q (CoQ) is a lipophilic antioxidant that is synthesized by a mitochondrial complex integrated by at least ten nuclear encoded COQ gene products. CoQ increases cell survival under different stress conditions, including mitochondrial DNA (mtDNA) depletion and treatment with cancer drugs such as camptothecin (CPT). We have previously demonstrated that CPT induces CoQ biosynthesis in mammal cells.


RESULTS
CPT activates NF-kappaB that binds specifically to two kappaB binding sites present in the 5'-flanking region of the COQ7 gene. This binding is functional and induces both the COQ7 expression and CoQ biosynthesis. The inhibition of NF-kappaB activation increases cell death and decreases both, CoQ levels and COQ7 expression induced by CPT. In addition, using a cell line expressing very low of NF-kappaB, we demonstrate that CPT was incapable of enhancing enhance both CoQ biosynthesis and COQ7 expression in these cells.


CONCLUSIONS
We demonstrate here, for the first time, that a transcriptional mechanism mediated by NF-kappaB regulates CoQ biosynthesis. This finding contributes new data for the understanding of the regulation of the CoQ biosynthesis pathway.
Brea-Calvo
Gloria
G
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC and Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Sevilla, Spain.
Siendones
Emilio
E
Sánchez-Alcázar
José A
JA
de Cabo
Rafael
R
Navas
Plácido
P
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D001665:Binding Sites; D002166:Camptothecin / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014451:Ubiquinone / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D014451:Ubiquinone; C030777:ubiquinone 7; D002166:Camptothecin