The role of VIT1/FBXO11 in the regulation of apoptosis and tyrosinase export from endoplasmic reticulum in cultured melanocytes.
Our previous study has shown that VIT1 gene in Chinese vitiligo patients is de facto the FBXO11 gene, and the silencing of that gene has an impact on the ultrastructure of melanocytes. In this study, we further identified the role of the FBXO11 gene in melanocytes and the relationship between dilated endoplasmic reticulum (ER) and tyrosinase by inhibition and overexpression of FBXO11 gene. Cell proliferation, apoptosis, cycle and migration of melanocytes were examined when the FBXO11 gene was silenced or overexpressed. The results showed that FBXO11 gene promoted cell proliferation and suppressed cell apoptosis, and yet had little effect on cell migration. Obvious swelling of ER was found in the cells transfected with siRNA of FBXO11 gene. Interestingly, protein level of tyrosinase was extraordinarily high following inhibition of FBXO11 gene. Further examination revealed that tyrosinase and calreticulin were co-localized in ER of transfected cells following siRNA of FBXO11 gene, suggesting that tyrosinase could not be exported from ER effectively. Collectively, our results support the notion that FBXO11 plays an important role in regulating proliferation and apoptosis of melanocytes, and functional export of tyrosinase from ER in vitiligo melanocytes.
Guan
Cuiping
C
Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou 310009, PR China.
Lin
Fuquan
F
Zhou
Miaoni
M
Hong
Weisong
W
Fu
Lifang
L
Xu
Wen
W
Liu
Dongyin
D
Wan
Yinsheng
Y
Xu
Aie
A
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D037282:Calreticulin / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D037282:Calreticulin; D044783:F-Box Proteins; D014442:Monophenol Monooxygenase; C457579:FBXO11 protein, human; D011484:Protein-Arginine N-Methyltransferases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9