Hypoxia induces expression of a GPI-anchorless splice variant of the prion protein.
The human prion protein (PrP) is a glycoprotein with a glycosylphosphatidylinositol (GPI) anchor at its C-terminus. Here we report alternative splicing within exon 2 of the PrP gene (PRNP) in the human glioblastoma cell line T98G. The open reading frame of the alternatively spliced mRNA lacked the GPI anchor signal sequence and encoded a 230 amino acid polypeptide. Its product, GPI-anchorless PrP (GPI(-) PrPSV), was unglycosylated and soluble in non-ionic detergent, and was found in the cytosolic fraction. We also detected low levels of alternatively spliced mRNA in human brain and non-neuronal tissues. When long-term passaged T98G cells were placed in a low-oxygen environment, alternatively spliced mRNA expression increased and expression of normally spliced PrP mRNA decreased. These findings imply that oxygen tension regulates GPI(-) PrPSV expression in T98G cells.
Kikuchi
Yutaka
Y
Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan. kikuchi@nihs.go.jp
Kakeya
Tomoshi
T
Nakajima
Osamu
O
Sakai
Ayako
A
Ikeda
Kikuko
K
Yamaguchi
Naoto
N
Yamazaki
Takeshi
T
Tanamoto
Ken-ichi
K
Matsuda
Haruo
H
Sawada
Jun-ichi
J
Takatori
Kosuke
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D005091:Exons; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000737:chemistry; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D007477:Ions; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000235:genetics*; D017434:Protein Structure, Tertiary
D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; D007477:Ions; D011328:Prions