Abstract
APR3 (apoptosis related protein 3) is a novel gene highly conserved across species. Analysis of the data about APR3 available at GEO profiles revealed consistent and significant changes of APR3 expression level in certain developmental and inflammatory processes. Based on the search and analysis of all the submitted mRNA sequence, we postulated that the two transcripts may arise from separate promoter activities rather than previously assumed alternative splicing. Through reporter assay and PCR data, we identified the distinct promoters for the two transcripts of APR3. Furthermore, exogenous expression of a constitutively active mutant of transcription factor NFAT was able to enhance both the promoter activities of APR3. Sequential deletion of the promoter from the 5′ side and mutation of the promoter suggested the functional NFAT binding sites might localize between −96 bp and −47 bp. In contrast, exogenous expression of a constitutively active mutant of the transcription factor NFkB inhibited APR3 transcription. Our data suggested that APR3 might be functionally important in certain processes under which NFAT and/or NFκB are/is activated.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Zhu F, Yan W, Zhao ZL, Chai YB, Lu F, Wang Q, Peng WD, Yang AG, Wang CJ (2000) Improved PCR-based subtractive hybridization strategy for cloning differentially expressed genes. Biotechniques 29(2):310–313
Macian F (2005) NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol 5:472–484
Porter CM, Clipstone NA (2002) Sustained NFAT signaling promotes a Th1-like pattern of gene expression in primary murine CD4 + T cells. J Immunol 168:4936–4945
Adachi S, Amasaki Y, Miyatake S, Arai N, Iwata M (2000) Successive expression and activation of NFAT family members during thymocyte differentiation. J Biol Chem 275:14708–14716
Siebenlist U, Brown K, Claudio E (2005) Control of lymphocyte development by nuclear factor-kappaB. Nat Rev Immunol 5:435–445
Habraken Y, Piette J (2006) NF-kappaB activation by double-strand breaks. Biochem Pharmacol 72:1132–1141
Magne N, Toillon RA, Bottero V, Didelot C, Houtte PV, Gerard JP, Peyron JF (2006) NF-kappaB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett 231:158–168
Zhang G, Ghosh S (2000) Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through Toll-like receptors. J Endotoxin Res 6:453–457
Schug J, Christian Overton G (1997) Technical Report CBIL-TR-1997-1001-v0.0 Computational Biology and Informatics URL: http://www.cbil.upenn.edu/tess
Fu H, Yang G, Lu F, Wang R, Yao L, Lu Z (2006) Transcriptional up-regulation of restin by all-trans retinoic acid through STAT1 in cancer cell differentiation process. Biochem Biophys Res Commun 343:1009–1016
Breathnach R, Chambon P (1981) Organization and expression of eucaryotic split genes coding for proteins. Ann Rev Biochem 50:349–383
Santini MP, Talora C, Seki T, Bolgan L, Dotto GP (2001) Cross talk among calcineurin, Sp1/Sp3, and NFAT in control of p21 (WAF1/CIP1) expression in keratinocyte differentiation. Proc Natl Acad Sci USA 98:9575–9580
Gonzalez Bosc LV, Layne JJ, Nelson MT, Hill-Eubanks DC (2005) Nuclear factor of activated T cells and serum response factor cooperatively regulate the activity of an alpha-actin intronic enhancer. J Biol Chem 280:26113–26120
Youn HD, Chatila TA, Liu JO (2000) Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis. EMBO J 19:4323–4331
Cilloni D, Messa F, Arruga F, Defilippi I, Morotti A, Messa E, Carturan S, Giugliano E, Pautasso M, Bracco E, Rosso V, Sen A, Martinelli G, Baccarani M, Saglio G (2006) The NF-kappaB pathway blockade by the IKK inhibitor PS1145 can overcome imatinib resistance. Leukemia 20(1):61–67 Jan
Sica A, Dorman L, Viggiano V, Cippitelli M, Ghosh P, Rice N, Young HA (1997) Interaction of NF-kappaB and NFAT with the interferon-gamma promoter. J Biol Chem 272:30412–30420
Anderson HD, Rahmutula D, Gardner DG (2004) Tumor necrosis factor-alpha inhibits endothelial nitric-oxide synthase gene promoter activity in bovine aortic endothelial cells. J Biol Chem 279:963–969
Zheng PZ, Wang KK, Zhang QY, Huang QH, Du YZ, Zhang QH, Xiao DK, Shen SH, Imbeaud S, Eveno E, Zhao CJ, Chen YL, Fan HY, Waxman S, Auffray C, Jin G, Chen SJ, Chen Z, Zhang J (2005) Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci USA 102:7653–7658
Wang J, Yen A (2004) A novel retinoic acid-responsive element regulates retinoic acid-induced BLR1 expression. Mol Cell Biol 24:2423–2443
Rao A, Luo C, Hogan PG (1997) Transcription factors of the NFAT family: regulation and function. Ann Rev Immunol 15:707–747
Serfling E, Berberich-Siebelt F, Avots A, Chuvpilo S, Klein-Hessling S, Jha MK, Kondo E, Pagel P, Schulze-Luehrmann J, Palmetshofer A (2004) NFAT and NF-kappaB factors-the distant relatives. Int J Biochem Cell Biol 36:1166–1170
Acknowledgments
We thank Dr. Lin LI, Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Dr Haian Fu, Emory University, USA; Dr Ran Ruiqiong, MIND Institute and Department of Neurology, University of California at Davis; for their kind gifts. This work was supported by National Science Fund of China (NSF:30470387), Chinese Military Fund for Distinguished Youth (Grant NO.424137095) and Program for Changjiang Scholars and Innovative Research Team in University (IRT0459).
Author information
Authors and Affiliations
Corresponding authors
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s11010-007-9572-9
Rights and permissions
About this article
Cite this article
Yang, G., Yu, F., Fu, H. et al. Identification of the distinct promoters for the two transcripts of apoptosis related protein 3 and their transcriptional regulation by NFAT and NFκB. Mol Cell Biochem 302, 187–194 (2007). https://doi.org/10.1007/s11010-007-9440-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-007-9440-7