Identification and characterization of endoplasmic reticulum-associated protein, ERp43.
Disposal of misfolded proteins from the lumen of the endoplasmic reticulum (ER) is one of the quality control mechanisms present in the protein secretory pathway. Through ER-associated degradation, misfolded substrates are targeted to the cytosol where they are degraded by proteasomes. Here we describe the identification of a human ER-associated 43-kD protein (ERp43) by sequencing of the subtraction suppression hybridization cDNA library from ER stress-treated cells. The ERp43 gene encodes a protein of 383 amino acid residues that contains a potential transmembrane domain. Analysis revealed that ERp43 is primarily located in the ER. Quantitative reverse transcriptase-polymerase chain reaction demonstrated that gene expression was relatively high in the neuronal tissues and in the kidney, with ERp43 protein highly expressed in the spinal cord and in the kidney. In cultured cells, overexpression of ERp43 accelerated cell growth and inhibited ER stress-induced cell death, while down-regulation of ERp43 expression decreased proliferation rate and enhanced this type of cell death. These findings indicate that ERp43 plays important roles in cell growth and ER stress-induced cell death.
Nishikawa
Manabu
M
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, Osaka 545-8585, Japan. nishikawa@med.osaka-cu.ac.jp
Kira
Yukimi
Y
Yabunaka
Yoriko
Y
Inoue
Masayasu
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D051381:Rats
C515307:ERGIC-53 protein, mouse; C517615:ERGIC3 protein, human; C084004:LMAN1 protein, human; C501458:Lman1 protein, rat; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins