SIRT2 Affects Primary Cilia Formation by Regulating mTOR Signaling in Retinal Pigmented Epithelial Cells

SIRT2, a member of the Class III HDAC family, participates in diverse cellular processes and regulates several pathological conditions. Although a few reports show that SIRT2 regulates the cell cycle, the causes and outcomes of SIRT2-dependent cell proliferation remain unclear. Here, we examined the...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-03, Vol.21 (6), p.2240
Main Authors: Lim, Jeaho, Son, Juyoung, Ryu, Jaewook, Kim, Ja-Eun
Format: Article
Language:English
Subjects:
Autophagy
Benzamides - pharmacology
Cell Cycle
Cell growth
Cell Line
Cell proliferation
Cilia
Cilia - metabolism
Enzyme Inhibitors - pharmacology
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - metabolism
G1 phase
Growth factors
Histone deacetylase
Humans
Inhibitors
Kinases
Motility
mtor
Oxidative stress
Proteins
Rapamycin
Retina
Retinal Pigment Epithelium - cytology
Retinal Pigment Epithelium - metabolism
Signal Transduction
siRNA
sirt2
Sirtuin 2 - antagonists & inhibitors
Sirtuin 2 - genetics
Sirtuin 2 - metabolism
Sulfonamides - pharmacology
TOR protein
TOR Serine-Threonine Kinases - metabolism
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Summary:SIRT2, a member of the Class III HDAC family, participates in diverse cellular processes and regulates several pathological conditions. Although a few reports show that SIRT2 regulates the cell cycle, the causes and outcomes of SIRT2-dependent cell proliferation remain unclear. Here, we examined the effects of SIRT2 suppression in human RPE1 cells using siRNA targeting SIRT2, and AK-1, a SIRT2-specific inhibitor. The number of primary cilia in SIRT2-suppressed cells increased under serum-present conditions. Suppressing SIRT2 induced cell cycle arrest at G0/G1 phase by inactivating mammalian target of rapamycin (mTOR) signaling, possibly through mTORC1. Treatment with torin 1, an inhibitor of mTORC1/mTORC2, yielded results similar to those observed after SIRT2 suppression. However, SIRT2 suppression did not affect primary cilia formation or mTOR signaling following serum starvation. This suggests that SIRT2 acts as a critical sensor that links growth factor-dependent signal transduction and primary cilia formation by regulating the cell cycle.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21062240