Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway
Abstract
Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However, canonical and non-canonical functions of ACOT7 remain to be discovered. In this study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the p53-p21 signaling pathway without a DNA damage response. PKCζ was specifically involved in ACOT7 depletion-mediated cell cycle arrest as an upstream molecule of the p53-p21 signaling pathway in MCF7 human breast carcinoma and A549 human lung carcinoma cells. Of the other members of the ACOT family, including ACOT1, 4, 8, 9, 11, 12, and 13 that were expressed in human, ACOT4, 8, and 12 were responsive to genotoxic stresses. However, none of those had a role in cytostasis via activation of the PKCζ-p53-p21 signaling pathway. Analysis of the ACOT7 prognostic value revealed that low ACOT7 levels prolonged overall survival periods in breast and lung cancer patients. Furthermore, ACOT7 mRNA levels were higher in lung cancer patient tissues compared to normal tis...Continue Reading
References
Differential regulation of p53 function by protein kinase C isoforms revealed by a yeast cell system
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