PMID- 11284916 OWN - NLM STAT- MEDLINE DCOM- 20010419 LR - 20200315 IS - 0960-7722 (Print) IS - 1365-2184 (Electronic) IS - 0960-7722 (Linking) VI - 34 IP - 1 DP - 2001 Feb TI - SERCA activity is required for timely progression through G1/S. PG - 15-30 AB - Changes in intracellular Ca2+ correlate with specific events in the cell cycle. Here we investigated the role of Ca2+ in the G1 phase. HEK 293 cells were arrested in mitosis and subjected to short-term treatments that alter Ca2+ homeostasis prior to their release into G1. Treatment with thapsigargin (TG), an irreversible inhibitor of the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) lengthened the G1 phase. Moreover, TG treatment also resulted in a dramatic alteration in cellular morphology and attachment and in the reduction of MAPK activity and lower levels of cyclin D1 and cyclin E proteins. Treatments with reagents that transiently increase or decrease cytosolic Ca2+ or that temporarily inactivate SERCA did not alter any of the above parameters. Cells expressing a TG-resistant form of SERCA progressed normally through the G1/S transition after TG treatment. These results suggest that long-term SERCA inactivation affects cell cycle-dependent events and compromises progression through G1/S. FAU - Simon, V R AU - Simon VR AD - Banting and Best Department of Medical Research, University of Toronto, ON, Canada. simon_viviana@hotmail.com FAU - Moran, M F AU - Moran MF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 0 (Cyclin E) RN - 136601-57-5 (Cyclin D1) RN - 67526-95-8 (Thapsigargin) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - Calcium/metabolism MH - Calcium-Transporting ATPases/*metabolism MH - Cell Line MH - Cyclin D1/metabolism MH - Cyclin E/metabolism MH - *G1 Phase/drug effects MH - Humans MH - Mitogen-Activated Protein Kinases/metabolism MH - *S Phase/drug effects MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases MH - Thapsigargin/pharmacology PMC - PMC6495481 EDAT- 2001/04/04 10:00 MHDA- 2001/04/21 10:01 PMCR- 2001/12/20 CRDT- 2001/04/04 10:00 PHST- 2001/04/04 10:00 [pubmed] PHST- 2001/04/21 10:01 [medline] PHST- 2001/04/04 10:00 [entrez] PHST- 2001/12/20 00:00 [pmc-release] AID - cpr192 [pii] AID - CPR192 [pii] AID - 10.1046/j.1365-2184.2001.00192.x [doi] PST - ppublish SO - Cell Prolif. 2001 Feb;34(1):15-30. doi: 10.1046/j.1365-2184.2001.00192.x.