Open AccessCompetitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment.
Author(s) -
X A Li,
Amy Lee
Publication year - 1991
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.11.7.3446
Subject(s) - endoplasmic reticulum , biology , tunicamycin , chinese hamster ovary cell , unfolded protein response , viability assay , gene , microbiology and biotechnology , ionophore , cell culture , biochemistry , genetics , membrane
GRP78, a 78-kDa protein localized in the endoplasmic reticulum (ER), has been implicated in protein processing and stress protection. Its promoter contains a 36-bp region which is conserved among GRP genes across species and has the ability to compete for trans-acting factors mediating GRP gene expression. Integration of about 800 tandem copies of this sequence into the genome of a Chinese hamster ovary cell line (DG44) results in transfectants with the following phenotypes: (i) the induction level of GRP78 by the calcium ionophore A23187 and tunicamycin is reduced 4- and 2-fold, respectively, (ii) the induction levels of two other ER luminal protein genes, GRP94 and ERp72, are simultaneously down-regulated, (iii) the growth rate of these cells is half that of transfectants without the amplified sequence, and (iv) cell viability is decreased by 25-fold after A23187 treatment. These results provide new evidence that ERp72 shares common trans-acting regulatory factors with the GRP genes and that a reduction of this set of ER proteins correlates with lower viability after ionophore treatment.