CAR-mediated repression of Cdkn1a(p21) is accompanied by the Akt activation

Andrei A. Yarushkin, Mark E. Mazin, Anastasia Y. Yunusova, Kseniya V. Korchagina, Yuliya A. Pustylnyak, Elena A. Prokopyeva, Vladimir O. Pustylnyak

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)361-366
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume504
Issue number2
DOIs
Publication statusPublished - 2 Oct 2018

Keywords

  • Akt
  • Cdkn1a(p21)
  • Constitutive androstane receptor
  • Liver
  • PTEN
  • TCPOBOP
  • FORKHEAD TRANSCRIPTION FACTOR
  • MOUSE LIVERS
  • HEPATECTOMY
  • C-MYC
  • FOXO1
  • CONSTITUTIVE ANDROSTANE RECEPTOR
  • LIVER-REGENERATION
  • FACTOR FKHR
  • CELL-CYCLE
  • EXPRESSION
  • Cell Proliferation
  • Forkhead Box Protein O1/metabolism
  • Male
  • Proto-Oncogene Proteins c-akt/metabolism
  • Liver/metabolism
  • Cyclin-Dependent Kinase Inhibitor p21/metabolism
  • Promoter Regions, Genetic
  • Signal Transduction
  • Mice, Inbred C57BL
  • Receptors, Cytoplasmic and Nuclear/metabolism
  • Animals
  • Hepatocytes/cytology
  • Mice
  • Apoptosis

Fingerprint Dive into the research topics of 'CAR-mediated repression of Cdkn1a(p21) is accompanied by the Akt activation'. Together they form a unique fingerprint.

Cite this