• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Sep 15, 1999; 342(Pt 3): 683–689.
PMCID: PMC1220510

Expression of translationally controlled tumour protein is regulated by calcium at both the transcriptional and post-transcriptional level.


We have investigated how the programme of protein synthesis is altered in response to a loss of calcium homoeostasis in Cos-7 cells using a differential proteome mapping approach. Exposure of the cells to the calcium ionophore A23187 or thapsigargin, or alternatively, expression of a viral glycoprotein reported to deplete intracellular calcium stores, resulted in the up-regulated expression of a characteristic set of proteins. One of these is the translationally controlled tumour protein (TCTP), a cytoplasmic protein whose expression has not previously been linked to calcium perturbation. Quantitative Northern blot assay demonstrated that steady-state mRNA abundance of TCTP was also increased under these conditions. Clamping the cytosolic calcium concentration by the introduction of bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid (BAPTA) into cells did not affect the increase in steady-state levels of TCTP mRNA observed in response to ionophore. Therefore depletion of endoplasmic reticulum (ER) calcium, but not elevation of the cytosolic calcium concentration, was responsible for increased transcription of the TCTP gene. However, the presence of BAPTA significantly attenuated the ionophore-mediated increase in levels of the protein. Moreover, the level of TCTP in ionophore-treated cells increased in advance of a detectable increase in the corresponding mRNA abundance. These results indicate that expression of TCTP is regulated at two distinct levels in response to the concentration of calcium in different cellular compartments. Whereas depletion of the ER store causes an increase in TCTP mRNA abundance, increased cytosolic calcium concentrations regulate gene expression at the post-transcriptional level.

Full Text

The Full Text of this article is available as a PDF (372K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Meldolesi J, Pozzan T. The endoplasmic reticulum Ca2+ store: a view from the lumen. Trends Biochem Sci. 1998 Jan;23(1):10–14. [PubMed]
  • Gmitter D, Brostrom CO, Brostrom MA. Translational suppression by Ca2+ ionophores: reversibility and roles of Ca2+ mobilization, Ca2+ influx, and nucleotide depletion. Cell Biol Toxicol. 1996 Apr;12(2):101–113. [PubMed]
  • Pozzan T, Rizzuto R, Volpe P, Meldolesi J. Molecular and cellular physiology of intracellular calcium stores. Physiol Rev. 1994 Jul;74(3):595–636. [PubMed]
  • Fasolato C, Innocenti B, Pozzan T. Receptor-activated Ca2+ influx: how many mechanisms for how many channels? Trends Pharmacol Sci. 1994 Mar;15(3):77–83. [PubMed]
  • Fasolato C, Pizzo P, Pozzan T. Delayed activation of the store-operated calcium current induced by calreticulin overexpression in RBL-1 cells. Mol Biol Cell. 1998 Jun;9(6):1513–1522. [PMC free article] [PubMed]
  • Trump BF, Berezesky IK. The role of altered [Ca2+]i regulation in apoptosis, oncosis, and necrosis. Biochim Biophys Acta. 1996 Oct 11;1313(3):173–178. [PubMed]
  • Pahl HL, Baeuerle PA. Endoplasmicreticulum-induced signal transduction and gene expression. Trends Cell Biol. 1997 Feb;7(2):50–55. [PubMed]
  • Little E, Ramakrishnan M, Roy B, Gazit G, Lee AS. The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications. Crit Rev Eukaryot Gene Expr. 1994;4(1):1–18. [PubMed]
  • Lièvremont JP, Rizzuto R, Hendershot L, Meldolesi J. BiP, a major chaperone protein of the endoplasmic reticulum lumen, plays a direct and important role in the storage of the rapidly exchanging pool of Ca2+. J Biol Chem. 1997 Dec 5;272(49):30873–30879. [PubMed]
  • Mery L, Mesaeli N, Michalak M, Opas M, Lew DP, Krause KH. Overexpression of calreticulin increases intracellular Ca2+ storage and decreases store-operated Ca2+ influx. J Biol Chem. 1996 Apr 19;271(16):9332–9339. [PubMed]
  • Pahl HL, Baeuerle PA. A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF-kappa B. EMBO J. 1995 Jun 1;14(11):2580–2588. [PMC free article] [PubMed]
  • Bartlett JD, Luethy JD, Carlson SG, Sollott SJ, Holbrook NJ. Calcium ionophore A23187 induces expression of the growth arrest and DNA damage inducible CCAAT/enhancer-binding protein (C/EBP)-related gene, gadd153. Ca2+ increases transcriptional activity and mRNA stability. J Biol Chem. 1992 Oct 5;267(28):20465–20470. [PubMed]
  • Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 1998 Apr 1;12(7):982–995. [PMC free article] [PubMed]
  • Wang XZ, Kuroda M, Sok J, Batchvarova N, Kimmel R, Chung P, Zinszner H, Ron D. Identification of novel stress-induced genes downstream of chop. EMBO J. 1998 Jul 1;17(13):3619–3630. [PMC free article] [PubMed]
  • Kruman II, Nath A, Mattson MP. HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp Neurol. 1998 Dec;154(2):276–288. [PubMed]
  • Michelangeli F, Ruiz MC, del Castillo JR, Ludert JE, Liprandi F. Effect of rotavirus infection on intracellular calcium homeostasis in cultured cells. Virology. 1991 Apr;181(2):520–527. [PubMed]
  • Aldabe R, Irurzun A, Carrasco L. Poliovirus protein 2BC increases cytosolic free calcium concentrations. J Virol. 1997 Aug;71(8):6214–6217. [PMC free article] [PubMed]
  • van Kuppeveld FJ, Hoenderop JG, Smeets RL, Willems PH, Dijkman HB, Galama JM, Melchers WJ. Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release. EMBO J. 1997 Jun 16;16(12):3519–3532. [PMC free article] [PubMed]
  • Pérez JF, Chemello ME, Liprandi F, Ruiz MC, Michelangeli F. Oncosis in MA104 cells is induced by rotavirus infection through an increase in intracellular Ca2+ concentration. Virology. 1998 Dec 5;252(1):17–27. [PubMed]
  • Tian P, Estes MK, Hu Y, Ball JM, Zeng CQ, Schilling WP. The rotavirus nonstructural glycoprotein NSP4 mobilizes Ca2+ from the endoplasmic reticulum. J Virol. 1995 Sep;69(9):5763–5772. [PMC free article] [PubMed]
  • Tian P, Ball JM, Zeng CQ, Estes MK. Rotavirus protein expression is important for virus assembly and pathogenesis. Arch Virol Suppl. 1996;12:69–77. [PubMed]
  • Xu A, Bellamy AR, Taylor JA. BiP (GRP78) and endoplasmin (GRP94) are induced following rotavirus infection and bind transiently to an endoplasmic reticulum-localized virion component. J Virol. 1998 Dec;72(12):9865–9872. [PMC free article] [PubMed]
  • Both GW, Siegman LJ, Bellamy AR, Atkinson PH. Coding assignment and nucleotide sequence of simian rotavirus SA11 gene segment 10: location of glycosylation sites suggests that the signal peptide is not cleaved. J Virol. 1983 Nov;48(2):335–339. [PMC free article] [PubMed]
  • Bergmann CC, Maass D, Poruchynsky MS, Atkinson PH, Bellamy AR. Topology of the non-structural rotavirus receptor glycoprotein NS28 in the rough endoplasmic reticulum. EMBO J. 1989 Jun;8(6):1695–1703. [PMC free article] [PubMed]
  • Chen X, Easton D, Oh HJ, Lee-Yoon DS, Liu X, Subjeck J. The 170 kDa glucose regulated stress protein is a large HSP70-, HSP110-like protein of the endoplasmic reticulum. FEBS Lett. 1996 Feb 12;380(1-2):68–72. [PubMed]
  • Füllekrug J, Sönnichsen B, Wünsch U, Arseven K, Nguyen Van P, Söling HD, Mieskes G. CaBP1, a calcium binding protein of the thioredoxin family, is a resident KDEL protein of the ER and not of the intermediate compartment. J Cell Sci. 1994 Oct;107(Pt 10):2719–2727. [PubMed]
  • Krause KH, Michalak M. Calreticulin. Cell. 1997 Feb 21;88(4):439–443. [PubMed]
  • Gachet Y, Lee M, Sawitzki B, Tournier S, Poulton T, Bommer UA. Intracellular colocalisation of the translationally controlled protein P23 with cytoskeletal structures. Biochem Soc Trans. 1997 May;25(2):269S–269S. [PubMed]
  • Sanchez JC, Schaller D, Ravier F, Golaz O, Jaccoud S, Belet M, Wilkins MR, James R, Deshusses J, Hochstrasser D. Translationally controlled tumor protein: a protein identified in several nontumoral cells including erythrocytes. Electrophoresis. 1997 Jan;18(1):150–155. [PubMed]
  • Böhm H, Gross B, Gaestel M, Bommer UA, Ryffel G, Bielka H. The 5'-untranslated region of p23 mRNA from the Ehrlich ascites tumor is involved in translation control of the growth related protein p23. Biomed Biochim Acta. 1991;50(12):1193–1203. [PubMed]
  • Bommer UA, Lazaris-Karatzas A, De Benedetti A, Nürnberg P, Benndorf R, Bielka H, Sonenberg N. Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E. Cell Mol Biol Res. 1994;40(7-8):633–641. [PubMed]
  • Yenofsky R, Cereghini S, Krowczynska A, Brawerman G. Regulation of mRNA utilization in mouse erythroleukemia cells induced to differentiate by exposure to dimethyl sulfoxide. Mol Cell Biol. 1983 Jul;3(7):1197–1203. [PMC free article] [PubMed]
  • Chitpatima ST, Makrides S, Bandyopadhyay R, Brawerman G. Nucleotide sequence of a major messenger RNA for a 21 kilodalton polypeptide that is under translational control in mouse tumor cells. Nucleic Acids Res. 1988 Mar 25;16(5):2350–2350. [PMC free article] [PubMed]
  • Walsh BJ, Gooley AA, Williams KL, Breit SN. Identification of macrophage activation associated proteins by two-dimensional gel electrophoresis and microsequencing. J Leukoc Biol. 1995 Mar;57(3):507–512. [PubMed]
  • Böhm H, Benndorf R, Gaestel M, Gross B, Nürnberg P, Kraft R, Otto A, Bielka H. The growth-related protein P23 of the Ehrlich ascites tumor: translational control, cloning and primary structure. Biochem Int. 1989 Aug;19(2):277–286. [PubMed]
  • Stürzenbaum SR, Kille P, Morgan AJ. Identification of heavy metal induced changes in the expression patterns of the translationally controlled tumour protein (TCTP) in the earthworm Lumbricus rubellus1. Biochim Biophys Acta. 1998 Jul 9;1398(3):294–304. [PubMed]
  • Thiele H, Berger M, Lenzner C, Kühn H, Thiele BJ. Structure of the promoter and complete sequence of the gene coding for the rabbit translationally controlled tumor protein (TCTP) P23. Eur J Biochem. 1998 Oct 1;257(1):62–68. [PubMed]
  • Baudet C, Perret E, Delpech B, Kaghad M, Brachet P, Wion D, Caput D. Differentially expressed genes in C6.9 glioma cells during vitamin D-induced cell death program. Cell Death Differ. 1998 Jan;5(1):116–125. [PubMed]
  • Klausner RD, Rouault TA, Harford JB. Regulating the fate of mRNA: the control of cellular iron metabolism. Cell. 1993 Jan 15;72(1):19–28. [PubMed]
  • Chang SC, Erwin AE, Lee AS. Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors. Mol Cell Biol. 1989 May;9(5):2153–2162. [PMC free article] [PubMed]
  • McCauliffe DP, Yang YS, Wilson J, Sontheimer RD, Capra JD. The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters. J Biol Chem. 1992 Feb 5;267(4):2557–2562. [PubMed]
  • Ting J, Lee AS. Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation. DNA. 1988 May;7(4):275–286. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links