{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:14:12Z","timestamp":1790021652335,"version":"4.0.1"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Grant Agency of Slovak Ministry of Education and Slovak Academy of Sciences (VEGA)","award":["2\/0159\/19, 2\/0157\/18, 2\/0157\/18, 2\/0070\/19, 2\/0122\/17"],"award-info":[{"award-number":["2\/0159\/19, 2\/0157\/18, 2\/0157\/18, 2\/0070\/19, 2\/0122\/17"]}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"publisher","award":["APVV-15-0303, APVV-14-0334"],"award-info":[{"award-number":["APVV-15-0303, APVV-14-0334"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Slovak Research Agency","award":["ITMS 26230120009"],"award-info":[{"award-number":["ITMS 26230120009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>P-glycoprotein (P-gp, ABCB1 member of the ABC (ATP-binding cassette) transporter family) localized in leukemia cell plasma membranes is known to reduce cell sensitivity to a large but well-defined group of chemicals known as P-gp substrates. However, we found previously that P-gp-positive sublines of L1210 murine leukemia cells (R and T) but not parental P-gp-negative parental cells (S) are resistant to the endoplasmic reticulum (ER) stressor tunicamycin (an N-glycosylation inhibitor). Here, we elucidated the mechanism of tunicamycin resistance in P-gp-positive cells. We found that tunicamycin at a sublethal concentration of 0.1 \u00b5M induced retention of the cells in the G1 phase of the cell cycle only in the P-gp negative variant of L1210 cells. P-gp-positive L1210 cell variants had higher expression of the ER stress chaperone GRP78\/BiP compared to that of P-gp-negative cells, in which tunicamycin induced larger upregulation of CHOP (C\/EBP homologous protein). Transfection of the sensitive P-gp-negative cells with plasmids containing GRP78\/BiP antagonized tunicamycin-induced CHOP expression and reduced tunicamycin-induced arrest of cells in the G1 phase of the cell cycle. Taken together, these data suggest that the resistance of P-gp-positive cells to tunicamycin is due to increased levels of GRP78\/BiP, which is overexpressed in both resistant variants of L1210 cells.<\/jats:p>","DOI":"10.3390\/cells9040890","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T03:58:39Z","timestamp":1586231919000},"page":"890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Overexpression of GRP78\/BiP in P-Glycoprotein-Positive L1210 Cells is Responsible for Altered Response of Cells to Tunicamycin as a Stressor of the Endoplasmic Reticulum"],"prefix":"10.3390","volume":"9","author":[{"given":"M\u00e1rio","family":"\u0160ere\u0161","sequence":"first","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Pavl\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viera","family":"Boh\u00e1\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Kyca","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Borovsk\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-9999","authenticated-orcid":false,"given":"Boris","family":"Lakato\u0161","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, 81237 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2174-786X","authenticated-orcid":false,"given":"Albert","family":"Breier","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"},{"name":"Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, 81237 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdena","family":"Sulov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1152\/physrev.1999.79.3.683","article-title":"Signal transduction from the endoplasmic reticulum to the cell nucleus","volume":"79","author":"Pahl","year":"1999","journal-title":"Physiol. 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