C. Caspersen et al., The sarco/endoplasmic reticulum calcium-ATPase 2b is an endoplasmic reticulum stress-inducible protein, J BIOL CHEM, 275(29), 2000, pp. 22363-22372
The sarco/endoplasmic reticulum calcium-ATPase (SERCA) translocates Ca2+ fr
om the cytosol to the lumen of the endoplasmic reticulum, This Ca2+ storage
is important for cellular processes such as calcium signaling and endoplas
mic reticulum (ER)-associated posttranslational protein modifications. We i
nvestigated the expression of the SERCA2 and SERCA3 isozymes in PC12 cells
exposed to agents interfering with different aspects of the posttranslation
al protein processing within the ER, thereby activating the ER stress-induc
ed unfolded protein response (UPR). All agents increased the SERCA2b mRNA l
evel 3-4-fold, in parallel with increasing mRNA levels for the EB stress ma
rker proteins BiP/GRP78 and CHOP/GADD153, In contrast, SERCA3 mRNA levels d
id not change. SERCA2b mRNA stability was not changed, indicating that the
mechanism of its up-regulation was transcriptional, in accordance with the
presence of ER stress response elements in the promoter region of the SERCA
2 gene, SERCA2b was also increased at the protein level upon ER stress trea
tments. Induction of ER stress by tunicamycin, dithiothreitol, or L-azetidi
ne 2-carboxylic acid did not result in depletion of ER calcium, showing tha
t such depletion was not necessary for up-regulation of SERCA2b expression
or UPR activation in general. We conclude that the SERCA2b expression can b
e controlled by the UPR pathway independently of ER Ca2+ depletion.