Cell Proliferation and Motility Are Inhibited by G1 Phase Arrest in 15-kDa Selenoprotein-Deficient Chang Liver Cells.
The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.
School of Biological Sciences, Seoul National University, Seoul, 151-742 Korea.|Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-742 Korea.
Jeyoung
J
Bang
School of Biological Sciences, Seoul National University, Seoul, 151-742 Korea.
Jang Hoe
JH
Huh
School of Biological Sciences, Seoul National University, Seoul, 151-742 Korea.
Ji-Woon
JW
Na
School of Biological Sciences, Seoul National University, Seoul, 151-742 Korea.
Qiao
Q
Lu
Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Bradley A
BA
Carlson
Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Ryuta
R
Tobe
Department of Biological Sciences, Towson University, Towson, MD 21252.
Petra A
PA
Tsuji
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Vadim N
VN
Gladyshev
Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Dolph L
DL
Hatfield
School of Biological Sciences, Seoul National University, Seoul, 151-742 Korea.|Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-742 Korea.|Institute of Molecular Biology and Genetics, Seoul National University, Seoul, 151-742 Korea.
Byeong Jae
BJ
Lee
D002460:Cell Line / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D016193:G1 Phase; D006801:Humans; D034741:RNA, Small Interfering / Q000378:metabolism; D051140:Selenoproteins / Q000172:deficiency* / Q000235:genetics
D034741:RNA, Small Interfering; C495238:SELENOF protein, human; D051140:Selenoproteins
15-kDa selenoprotein; cell cycle arrest; cell proliferation; cyclin E; selenium