Abstract
Adenovirus E1a proteins are potent and ubiquitously acting tumor suppressors in human tumor cells. Through interaction with CtBP (as well as other mechanisms), E1a protein sensitizes cells to several apoptotic responses including anoikis. This interaction also induces the expression of certain epithelial cell adhesion and cytoskeletal genes in various tumor cell lines. Functionally analogous results are observed in mouse embryo fibroblasts lacking CtBP1 and CtBP2 genes. These results implicate CtBP as a potential modulator of the epithelial-to-mesenchymal transition (EMT) as well as apoptosis.
Keywords
- Mouse Embryo Fibroblast
- Transcription Factor Snail
- Cytoskeletal Gene
- Binding Zinc Finger Protein
- Polycomb Repression Complex Protein
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2(6):442–454.
Frisch SM, Screaton RA. Anoikis mechanisms. Curr Opin Cell Biol 2001; 13(5):555–562.
Frisch SM, Mymryk JS. Adenovirus-5 E1A: Paradox and paradigm. Nat Rev Mol Cell Biol 2002; 3(6):441–452.
Frisch SM. Ela induces the expression of epithelial characteristics. J Cell Biol 1994; 127(4):1085–1096.
Grooteclaes ML, Frisch SM. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene 2000; 19(33):3823–3828.
Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 1994; 124(4):619–626.
Grooteclaes M, Deveraux Q, Hildebrand J et al. C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. Proc Natl Acad Sci USA 2003; 100(8):4568–4573.
Attardi LD, Reczek EE, Cosmas C et al. PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev 2000; 14(6):704–718.
Ihrie RA, Marques MR, Nguyen BT et al. Perp is a p63-regulated gene essential for epithelial integrity. Cell 2005; 120(6):843–856.
Stemmler MP, Hecht A, Kemler R. E-cadherin intron 2 contains cis-regulatory elements essential for gene expression. Development 2005; 132(5):965–976.
Frisch SM. The epithelial cell default-phenotype hypothesis and its implications for cancer. Bioessays 1997; 19(8):705–709.
Cano A, Perez-Moreno MA, Rodrigp I et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2000; 2(2):76–83.
Batlle E, Sancho E, Franci C et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2000; 2(2):84–89.
Hajra KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 2002; 62(6):1613–1618.
Comijn J, Berx G, Vermassen P et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 2001; 7(6):1267–1278.
Guaita S, Puig I, Franci C et al. Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. J Biol Chem 2002; 277(42):39209–39216.
Nardini M, Spano S, Cericola C et al. CtBP/BARS: A dual-function protein involved in transcription corepression and Golgi membrane fission. EMBO J 2003; 22(12):3122–3130.
Lin X, Sun B, Liang M et al. Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Mol Cell 2003; 11(5):1389–1396.
Kagey MH, Melhuish TA, Wotton D. The polycomb protein Pc2 is a SUMO E3. Cell 2003; 113(1):127–137.
Barnes CJ, Vadlamudi RK, Mishra SK et al. Functional inactivation of a transcriptional corepressor by a signaling kinase. Nat Struct Biol 2003; 10(8):622–628.
Schurmann A, Mooney AF, Sanders LC et al. p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis. Mol Cell Biol 2000; 20(2):453–461.
Zhang Q, Nottke A, Goodman RH. Homeodomain-interacting protein kinase-2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis. Proc Nad Acad Sci USA 2005; 102(8):2802–2807.
Jakobi R, McCarthy CC, Koeppel MA et al. Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation. J Biol Chem 2003; 278(40):38675–38685.
Malliri A, van Es S, Huveneers S et al. The Rac exchange factor Tiaml is required for the establishment and maintenance of cadherin-based adhesions. J Biol Chem 2004; 279(29):30092–30098.
Fjeld CC, Birdsong WT, Goodman RH. Differential binding of NAD+ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor. Proc Nad Acad Sci USA 2003; 100(16):9202–9207.
Zhang Q, Piston DW, Goodman RH. Regulation of corepressor function by nuclear NADH. Science 2002; 295(5561):1895–1897.
Balasubramanian P, Zhao LJ, Chinnadurai G. Nicotinamide adenine dinucleotide stimulates oligpmerization, interaction with adenovirus ElA and an intrinsic dehydrogenase activity of CtBP. FEBS Lett 2003; 537(1–3):157–160.
Mazurek S, Boschek C, Eigenbrodt E. The role of phosphometabolites in cell proliferation, energy metabolism and tumor therapy. J Bioenerg Biomemb 1997; 29:315–330.
Singer S, Souza K, Thilly WG. Pyruvate utilization, phosphocholine and adenosine triphosphate (ATP) are markers of human breast tumor progression: A 31P-and 13G-nudear magnetic resonance (NMR) spectroscopy study. Cancer Res 1995; 55(22):5140–5145.
Stubbs M, Rodrigues L, Howe FA et al. Metabolic consequences of a reversed pH gradient in rat tumors. Cancer Res 1994; 54(15):4011–4016.
Obi-Tabot ET, Hanrahan LM, Cachecho R et al. Changes in hepatocyte NADH fluorescence during prolonged hypoxia. J Surg Res 1993; 55(6):575–580.
Polyak K, Xia Y, Zweier JL et al. A model for p53-induced apoptosis. Nature 1997; 389(6648):300–305.
Esposti MD, Hatzinisiriou I, McLennan H et al. Bd-2 and mitochondrial oxygen radicals. New approaches with reactive oxygen species-sensitive probes. J Biol Chem 1999; 274(42):29831–29837.
Kowaltowski AJ, Vercesi AE, Fiskum G. Bcl-2 prevents mitochondrial permeability transition and cytochrome c release via maintenance of reduced pyridine nucleotides. Cell Death Differ 2000; 7(10):903–910.
Imai T, Horiuchi A, Wang C et al. Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. Am J Pathol 2003; 163(4):1437–1447.
Hamada F, Bienz M. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell 2004; 7(5):677–685.
Alpatov R, Munguba GC, Caton P et al. Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Mol Cell Biol 2004; 24(23):10223–10235.
Shi Y, Simmons MN, Seki T et al. Change in gene expression subsequent to induction of Pnn/DRS/memA: Increase in p21(cip1/waf1). Oncogene 2001; 20(30):4007–4018.
Shi Y, Ouyang P, Sugrue SP. Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function. Oncogene 2000; 19(2):289–297.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2007 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Frisch, S.M. (2007). CtBP. In: GtBP Family Proteins. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39973-7_4
Download citation
DOI: https://doi.org/10.1007/978-0-387-39973-7_4
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-39971-3
Online ISBN: 978-0-387-39973-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)