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Biomed Res Int. 2019 Sep 19;2019:2582401. doi: 10.1155/2019/2582401. eCollection 2019.

Polycystin-1 Inhibits Cell Proliferation through Phosphatase PP2A/B56α.

Author information

1
Department of Oncology and Haematology, The Second Hospital, Jilin University, Changchun 130041, China.
2
Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton T6G 2H7, Canada.
3
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430086, China.
4
Department of Radiotherapy, The Second Hospital, Jilin University, Changchun 130041, China.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is associated with a number of cellular defects such as hyperproliferation, apoptosis, and dedifferentiation. Mutations in polycystin-1 (PC1) account for ∼85% of ADPKD. Here, we showed that wild-type (WT) or mutant PC1 composed of the last five transmembrane (TM) domains and the C-terminus (termed PC1-5TMC) inhibits cell proliferation and protein translation, as well as the downstream effectors of mTOR, consistent with previous reports. Knockdown of B56α, a subunit of the protein phosphatase 2A (PP2A) complex, or application of PP2A inhibitor okadaic acid or calyculin A, abolished the inhibitory effect of PC1 and PC1-5TMC on proliferation, indicating that PP2A/B56α mediates the regulation of cell proliferation by PC1. In addition to the phosphorylated S6 and 4EBP1, B56α was also downregulated by PC1 and PC1-5TMC. Furthermore, the downregulation of B56α, which may be mediated by mTOR but not AKT, can account for the dependence of PC1-inhibited proliferation on PP2A.

PMID:
31641668
PMCID:
PMC6770331
DOI:
10.1155/2019/2582401
[Indexed for MEDLINE]
Free PMC Article

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