RRC ID 31695
Author Kikuchi Y, Kakeya T, Nakajima O, Sakai A, Ikeda K, Yamaguchi N, Yamazaki T, Tanamoto K, Matsuda H, Sawada J, Takatori K.
Title Hypoxia induces expression of a GPI-anchorless splice variant of the prion protein.
Journal FEBS J
Abstract 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.
Volume 275(11)
Pages 2965-76
Published 2008-6-1
DOI 10.1111/j.1742-4658.2008.06452.x
PII EJB6452
PMID 18445040
MeSH Alternative Splicing Amino Acid Sequence Cell Line, Tumor Cytosol / metabolism Exons Gene Expression Regulation* Glycoproteins / chemistry Glycosylphosphatidylinositols / metabolism* Humans Hypoxia* Ions Molecular Sequence Data Neurons / metabolism Prions / chemistry* Prions / genetics* Protein Structure, Tertiary
IF 4.392
Times Cited 20
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material hPrP 129M with signal sequences (RDB12404) hPrP 129V with signal sequences (RDB12405) hPrP129M in pTA2 (RDB06716) hPrP129V in pTA2 (RDB06717) hPrPSV129M in pTA2 (RDB06718) hPrPSV129V in pTA2 (RDB06719).