Acyl-CoA thioesterase 7 is involved in cell cycle progression viaregulation of PKC zeta-p53-p21 signaling pathway

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474281.do
DOI
10.1038/cddis.2017.202
Title
Acyl-CoA thioesterase 7 is involved in cell cycle progression viaregulation of PKC zeta-p53-p21 signaling pathway
Description
This work was supported by a grant awarded to J-SL from the BasicScience Research Program (No. 2014R1A2A1A11051988), Nuclear Research andDevelopment Program (No. 2012-M2B2B1-2012055637), and Medical ResearchCenter (MRC) (No. 201409392) through the National Research Foundation(NRF) funded by the Korean government (MSIP). This work was alsopartially supported by a grant from the NRF of Korea to SHJ(NRF-2015R1D1A1A01058110).
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. PKC zeta 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 PKC zeta-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 tissues. We also observed a synergistic effect of ACOT7 depletion in combination with either IR or doxorubicin on cell proliferation in breast and lung cancer cells. Together, our data suggest that a low level of ACOT7 may be involved, at least in part, in the prevention of human breast and lung cancer development via regulation of cell cycle progression.
provenance
Made available in Cube on 2018-09-28T10:41:54Z (GMT). No. of bitstreams: 0
language
English
author
Jung, Seung Hee
Lee, Hyung Chul
Hwang, Hyun Jung
Park, Hyun A.
Moon, Young-Ah
Kim, Bong Cho
Lee, Hyeong Min
Kim, Kwang Pyo
Kim, Yong-Nyun
Lee, Byung Lan
Lee, Jae Cheol
Ko, Young-Gyu
Park, Heon Joo
Lee, Jae-Seon
accessioned
2018-09-28T10:41:54Z
available
2018-09-28T10:41:54Z
issued
2017
citation
CELL DEATH & DISEASE(8)
issn
2041-4889
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474281.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345273981
Jurisdiction
Rep.of Korea
Project Name
KU Advanced Graduate Program for Life Science
rights
openAccess
type
article


Files in This Item

There are no attached files.