Promotion of liver growth by CAR is accompanied by Akt pathway activation and FoxM1-Nedd4-mediated repression of PTEN. / Yarushkin, Andrei A.; Mazin, Mark E.; Pustylnyak, Yuliya A. et al.
In: Archives of Biochemistry and Biophysics, Vol. 672, 108065, 15.09.2019, p. 108065.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Promotion of liver growth by CAR is accompanied by Akt pathway activation and FoxM1-Nedd4-mediated repression of PTEN
AU - Yarushkin, Andrei A.
AU - Mazin, Mark E.
AU - Pustylnyak, Yuliya A.
AU - Prokopyeva, Elena A.
AU - Pustylnyak, Vladimir O.
N1 - Publisher Copyright: © 2019 Elsevier Inc.
PY - 2019/9/15
Y1 - 2019/9/15
N2 - Recently, we reported that treatment with the mouse agonist of the constitutive androstane receptor (CAR), 1,4-bis benzene[2-(3,5-dichloropyridyloxy)] (TCPOBOP; a well-known hepatomitogen), reduced PTEN protein levels, leading to Akt activation. Hence, the present study was performed to demonstrate the role of CAR in PTEN regulation and liver growth. Liver hyperplasia caused by CAR activation was confirmed to be mediated by a decrease in PTEN protein level and the activation of the Akt signalling pathway in the liver of mice. Treatment with the CAR agonist decreased the PTEN levels and increased Foxm1 levels, which correlate with the elevated expression of the FoxM1 target gene, Nedd4-1, an E3 ligase involved in PTEN ubiquitination, and the promotion of degradation. The increase in Nedd4-1 levels was accompanied by an increase in CAR-mediated accumulation of Foxm1 on the Nedd4-1 gene promoter. Therefore, these results provide evidence that a notable function of CAR is its liver growth promotion effect, which is accompanied by FoxM1-Nedd4-mediated repression of PTEN and Akt pathway activation.
AB - Recently, we reported that treatment with the mouse agonist of the constitutive androstane receptor (CAR), 1,4-bis benzene[2-(3,5-dichloropyridyloxy)] (TCPOBOP; a well-known hepatomitogen), reduced PTEN protein levels, leading to Akt activation. Hence, the present study was performed to demonstrate the role of CAR in PTEN regulation and liver growth. Liver hyperplasia caused by CAR activation was confirmed to be mediated by a decrease in PTEN protein level and the activation of the Akt signalling pathway in the liver of mice. Treatment with the CAR agonist decreased the PTEN levels and increased Foxm1 levels, which correlate with the elevated expression of the FoxM1 target gene, Nedd4-1, an E3 ligase involved in PTEN ubiquitination, and the promotion of degradation. The increase in Nedd4-1 levels was accompanied by an increase in CAR-mediated accumulation of Foxm1 on the Nedd4-1 gene promoter. Therefore, these results provide evidence that a notable function of CAR is its liver growth promotion effect, which is accompanied by FoxM1-Nedd4-mediated repression of PTEN and Akt pathway activation.
KW - Akt
KW - Constitutive androstane receptor
KW - FoxM1
KW - Liver
KW - Nedd4-1
KW - PTEN
KW - NEDD4-1
KW - UBIQUITIN LIGASE
KW - HEPATECTOMY
KW - REGENERATION
KW - CELL-SURVIVAL
KW - NUCLEAR RECEPTOR
KW - INHIBITION
KW - CONSTITUTIVE ANDROSTANE RECEPTOR
KW - TUMOR-SUPPRESSOR
KW - EXPRESSION
UR - http://www.scopus.com/inward/record.url?scp=85071788077&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2019.108065
DO - 10.1016/j.abb.2019.108065
M3 - Article
C2 - 31394088
AN - SCOPUS:85071788077
VL - 672
SP - 108065
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
M1 - 108065
ER -
ID: 21466307