title: Cab45S promotes cell proliferation through SERCA2b inhibition and Ca2+ signaling.
abstract: Cytosolic Ca(2+), closely related to endoplasmic reticulum (ER) Ca(2+), plays a critical role in regulating cell proliferation and tumorigenesis. However, the role of ER lumen proteins in regulating cytosolic Ca(2+) level remains poorly understood. Here, we find that the Cab45S, localizes in the ER lumen, inhibits sarco/ER Ca(2+)-ATPase 2b (SERCA2b) activity through its first EF-hand domain directly binding to the intra-lumenal loop 4 of SERCA2b, and reduces ER Ca(2+). STIM1 activation, induced by the Cab45S-dependent drop in ER Ca(2+), together with the upregulation of the plasma membrane Ca(2+) channel TRPC1 ultimately increases extracellular Ca(2+) influx. Furthermore, increased cytosolic Ca(2+) level elicits Ca(2+)-NFAT signaling and promotes cell proliferation. Consistently, in cervical carcinoma patients, Cab45S is upregulated. Thus, our data reveal that the ability of Cab45S to inhibit SERCA2b activity is crucial for its role as a modulator of cell proliferation and tumor growth.
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Lu
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Yue
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Teng
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing, China.|Center for Quantitative Biology, Peking University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D020033:Protein Isoforms; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
chemical_list: D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins; D020033:Protein Isoforms; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; C099100:SDF4 protein, human; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium