CAR-mediated repression of Cdkn1a(p21) is accompanied by the Akt activation
- Novosibirsk State University, Novosibirsk, Pirogova Street, 1, 630090 (Russian Federation)
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 8 Lavrentjev Avenue, 630090 (Russian Federation)
Highlights: • CAR-mediated liver growth is accompanied by the decrease in PTEN. • CAR-mediated liver growth is accompanied by the Akt activation. • CAR-mediated Akt activation is accompanied by the decrease in Foxo1. • CAR activation decreased the level of p21. It was shown that CAR participates in the regulation of many cell processes. Thus, the activation of CAR causes a proliferating effect in the liver, which provides grounds to consider CAR as a therapeutic target when having a partial resection of this organ. Even though a lot of work has been done on the function of CAR in regulating hepatocyte proliferation, very little has been done on its complex mediating mechanism. This study, therefore, showed that the liver growth resulting from CAR activation leads to the decline in the level of PTEN protein and subsequent Akt activation in mouse liver. The increase of Akt activation produced by CAR agonist was accompanied by a decrease in the level of Foxo1, which was correlated with decreased expression of Foxo1 target genes, including Cdkn1a(p21). Moreover, the study also demonstrated that there exists a negative regulatory impact of CAR on the relationship between Foxo1 and targeted Cdkn1a(p21) promoter. Therefore, the study results revealed an essential function of CAR-Akt-Foxo1 signalling pathway in controlling hepatocyte proliferation by repressing the cell cycle regulator Cdkn1a (p21).
- OSTI ID:
- 23134209
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 504; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
MicroRNA-21 accelerates hepatocyte proliferation in vitro via PI3K/Akt signaling by targeting PTEN
Combination of PTEN and {gamma}-Ionizing Radiation Enhances Cell Death and G{sub 2}/M Arrest Through Regulation of AKT Activity and p21 Induction in Non-Small-Cell Lung Cancer Cells