adapt78, a stress-inducible mRNA, is related to the glucose-regulated protein family of genes.
We have recently reported a new oxidant- and calcium-inducible mRNA, adapt78, from hamster HA-1 cells. The adapt78 mRNA is induced in HA-1 cells under conditions where a protective adaptive response is observed and contains a translatable open reading frame whose protein product shows strong homology to a human sequence. Computer analysis of the predicted Adapt78 protein sequence also revealed a stretch of amino acids homologous to a portion of the glucose-regulated protein78 (Grp78). Based on this homology, we tested the hypothesis that adapt78 may be a new member of the grp gene family. Toward this, we assessed the modulation of adapt78 mRNA by stress agents known to induce grp78. In HA-1 cells, adapt78 mRNA was induced by the calcium ionophore A23187, 2-deoxyglucose, brefeldin A, tunicamycin, thapsigargin, and cyclopiazonic acid, with thapsigargin being the most potent inducer (7.3-fold). As expected, grp78 mRNA was also induced by these agents in our model system. In contrast, heat shock treatment produced little if any modulation of either grp78 or adapt78. Differences were also observed, as adapt78 mRNA but not grp78 mRNA was induced by 160 microM hydrogen peroxide, and adapt78 demonstrated earlier induction kinetics for certain agents compared with grp78. adapt78 mRNA was also found to be induced in several different human cell lines. A23187 had the strongest effect on adapt78 mRNA levels in human cells, inducing greater than 20-fold in all human cell cultures tested. Furthermore, in vitro transcription translation of human adapt78 cDNA produced an Adapt78 protein product. We conclude that adapt78 may be a new member of the grp family of genes and may represent an early response grp that complements the actions of grp78 and grp94.
Department of Biochemistry & Molecular Biology, The Albany Medical College, Albany, New York, 12208, USA.
K P
KP
Leahy
K J
KJ
Davies
M
M
Dull
J J
JJ
Kort
K W
KW
Lawrence
D R
DR
Crawford
D000595:Amino Acid Sequence; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D006224:Cricetinae; D003847:Deoxyglucose / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins; D006358:Hot Temperature; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007476:Ionophores; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; C018551:glucose-regulated proteins; D000001:Calcimycin; D003847:Deoxyglucose; D000252:Calcium-Transporting ATPases