A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors / 医学前沿

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

Hydrophobicity of the C-terminal GPI-anchor Attachment Signals Determines ER-associated Degradation Pathway of Precursor Proteins / 中国生物化学与分子生物学报

More than 150 glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are expressed in mammalian cells and involved in various physiological processes such as immune recognition, cell communication and signal transduction. GPI is transferred to proteins in the endoplasmic reticulum (ER). When GPI-anchoring is impaired, precursor proteins are thought to be degraded through ER-associated degradation (ERAD). However, the mechanism of their degradation in ERAD remains unclear. To investigate the impact of ERAD pathways on degradation of GPI precursor proteins, we used series of knockout (KO) human embryonic kidney 293 (HEK293) cells defective in PIGS gene, which encodes a GPI transamidase complex subunit, combined with KO in HRD1 (PIGS-HRD1-KO) or GP78 (PIGSGP78-KO), which encodes the E3 ubiquitin ligases for the ERAD pathways. We compared the stability of 16 GPI precursor proteins in the ERAD-deficient cells with the parental PIGS-KO cells. Western blotting data showed that the GPI precursor proteins were stabilized in either PIGS-HRD1-KO (I

Prostate stem cell antigen gene is expressed in islets of pancreas / 대한해부학회지

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored cell surface antigen with an organ-dependent expression pattern in cancers; e.g., up-regulated in prostate cancer and down-regulated in gastric cancer. Previously it was reported that PSCA is not expressed in the normal pancreas but aberrantly expressed in pancreatic cancer. In this present study, we identified PSCA expression in islets of the pancreas by immunohistochemistry, which was co-localized with four islet-cell markers: insulin, glucagon, somatostatin and pancreatic polypeptide. In our investigation of the transcription start site of PSCA, we found a non-coding splicing variant of PSCA as well as authentic PSCA transcripts in mRNA samples from a normal pancreas. Both the transcripts were also identified in several pancreatic cancer cell lines. We previously reported that PSCA expression is correlated to the methylation status of the enhancer region in gastric and gallbladder cancer cell lines but not in pancreatic cancer cell lines, suggesting that PSCA expression is regulated in a diff erent mode in pancreatic cancer from that in gastric and gallbladder cancers.