This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Buettner, R
Right arrow Articles by Tainsky, M A
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buettner, R
Right arrow Articles by Tainsky, M A

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 July; 13(7): 4174-4185

An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2.

R Buettner, P Kannan, A Imhof, R Bauer, S O Yim, R Glockshuber, M W Van Dyke and M A Tainsky

Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

ABSTRACT

AP-2 is a retinoic acid-inducible and developmentally regulated activator of transcription. We have cloned an alternative AP-2 transcript (AP-2B) from the human teratocarcinoma cell line PA-1, which encodes a protein differing in the C terminus from the previously isolated AP-2 protein (AP-2A). This protein contains the activation domain of AP-2 and part of the DNA binding domain but lacks the dimerization domain which is necessary for DNA binding. Analysis of overlapping genomic clones spanning the entire AP-2 gene proves that AP-2A and AP-2B transcripts are alternatively spliced from the same gene. Both transient and stable transfection experiments show that AP-2B inhibits AP-2 transactivator function, as measured by an AP-2-responsive chloramphenicol acetyltransferase reporter plasmid. Furthermore, constitutive AP-2B expression in PA-1 cells causes a retinoic acid-resistant phenotype, anchorage-independent growth in soft agar, and tumorigenicity in nude mice, in a fashion similar to transformation of these cells by oncogenes. To determine the mechanism by which AP-2B exerts its inhibitory function, we purified bacterially expressed AP-2A and AP-2B proteins. While bacterial AP-2B does not bind an AP-2 consensus site, it strongly inhibits binding of the endogenous AP-2 present in PA-1 cell nuclear extracts. However, DNA sequence-specific binding of bacterially expressed AP-2A cannot be inhibited by bacterially expressed AP-2B. Therefore, inhibition of AP-2 activity by the protein AP-2B may require an additional factor or modification supplied by nuclear extracts.

Mol Cell Biol. 1993 July; 13(7): 4174-4185




This article has been cited by other articles:

  • Iwamoto, N., Abe-Dohmae, S., Lu, R., Yokoyama, S. (2008). Involvement of Protein Kinase D in Phosphorylation and Increase of DNA Binding of Activator Protein 2{alpha} to Downregulate ATP-Binding Cassette Transporter A1. Arterioscler. Thromb. Vasc. Bio. 28: 2282-2287 [Abstract] [Full Text]  
  • Mannstadt, M., Bertrand, G., Muresan, M., Weryha, G., Leheup, B., Pulusani, S. R., Grandchamp, B., Juppner, H., Silve, C. (2008). Dominant-Negative GCMB Mutations Cause an Autosomal Dominant Form of Hypoparathyroidism. J. Clin. Endocrinol. Metab. 93: 3568-3576 [Abstract] [Full Text]  
  • Iwamoto, N., Abe-Dohmae, S., Ayaori, M., Tanaka, N., Kusuhara, M., Ohsuzu, F., Yokoyama, S. (2007). ATP-Binding Cassette Transporter A1 Gene Transcription Is Downregulated by Activator Protein 2{alpha}: Doxazosin Inhibits Activator Protein 2{alpha} and Increases High-Density Lipoprotein Biogenesis Independent of {alpha}1-Adrenoceptor Blockade. Circ. Res. 101: 156-165 [Abstract] [Full Text]  
  • Tran, Y. H., Xu, Z., Kato, A., Mistry, A. C., Goya, Y., Taira, M., Brandt, S. J., Hirose, S. (2006). Spliced Isoforms of LIM-Domain-Binding Protein (CLIM/NLI/Ldb) Lacking the LIM-Interaction Domain. J Biochem 140: 105-119 [Abstract] [Full Text]  
  • Douglas, D. B., Akiyama, Y., Carraway, H., Belinsky, S. A., Esteller, M., Gabrielson, E., Weitzman, S., Williams, T., Herman, J. G., Baylin, S. B. (2004). Hypermethylation of a Small CpGuanine-Rich Region Correlates with Loss of Activator Protein-2{alpha} Expression during Progression of Breast Cancer. Cancer Res. 64: 1611-1620 [Abstract] [Full Text]  
  • Wajapeyee, N., Somasundaram, K. (2003). Cell Cycle Arrest and Apoptosis Induction by Activator Protein 2{alpha} (AP-2{alpha}) and the Role of p53 and p21WAF1/CIP1 in AP-2{alpha}-mediated Growth Inhibition. J. Biol. Chem. 278: 52093-52101 [Abstract] [Full Text]  
  • Klootwijk, R, Hol, F A, Wu, M, Willemen, J J H T, Groenen, P, Hamel, B, Straatman, H, Steegers-Theunissen, R P M, Mariman, E C M, Franke, B (2003). Genetic variation analysis of MLP, TFAP2A, and CSK in patients with neural tube defects. J. Med. Genet. 40: e43-43 [Full Text]  
  • Ruiz, M., Troncoso, P., Bruns, C., Bar-Eli, M. (2001). Activator Protein 2{alpha} Transcription Factor Expression Is Associated with Luminal Differentiation and Is Lost in Prostate Cancer. Clin. Cancer Res. 7: 4086-4095 [Abstract] [Full Text]  
  • Nyormoi, O., Wang, Z., Doan, D., Ruiz, M., McConkey, D., Bar-Eli, M. (2001). Transcription Factor AP-2{alpha} Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor Alpha-Induced Apoptosis in Breast Cancer Cells. Mol. Cell. Biol. 21: 4856-4867 [Abstract] [Full Text]  
  • Kramer, P. R., Krishnamurthy, R., Mitchell, P. J., Wray, S. (2000). Transcription Factor Activator Protein-2 Is Required for Continued Luteinizing Hormone-Releasing Hormone Expression in the Forebrain of Developing Mice. Endocrinology 141: 1823-1838 [Abstract] [Full Text]  
  • Nakayama, T., Soma, M., Takahashi, Y., Rehemudula, D., Kanmatsuse, K., Furuya, K. (2000). Functional Deletion Mutation of the 5'-Flanking Region of Type A Human Natriuretic Peptide Receptor Gene and Its Association With Essential Hypertension and Left Ventricular Hypertrophy in the Japanese. Circ. Res. 86: 841-845 [Abstract] [Full Text]  
  • Shachaf, C., Skorecki, K. L., Tzukerman, M. (2000). Role of AP2 consensus sites in regulation of rat Npt2 (sodium-phosphate cotransporter) promoter. Am. J. Physiol. Renal Physiol. 278: F406-F416 [Abstract] [Full Text]  
  • LiCalsi, C., Christophe, S., Steger, D. J., Buescher, M., Fischer, W., Mellon, P. L. (2000). AP-2 family members regulate basal and cAMP-induced expression of human chorionic gonadotropin. Nucleic Acids Res 28: 1036-1043 [Abstract] [Full Text]  
  • Matsumura, T., Sakai, M., Matsuda, K., Furukawa, N., Kaneko, K., Shichiri, M. (1999). Cis-acting DNA Elements of Mouse Granulocyte/Macrophage Colony-stimulating Factor Gene Responsive to Oxidized Low Density Lipoprotein. J. Biol. Chem. 274: 37665-37672 [Abstract] [Full Text]  
  • Ren, Y., Reddy, S. A. G., Liao, W. S.-L. (1999). Purification and Identification of a Tissue-specific Repressor Involved in Serum Amyloid A1 Gene Expression. J. Biol. Chem. 274: 37154-37160 [Abstract] [Full Text]  
  • Langmann, T., Buechler, C., Ries, S., Schaeffler, A., Aslanidis, C., Schuierer, M., Weiler, M., Sandhoff, K., de Jong, P. J., Schmitz, G. (1999). Transcription factors Sp1 and AP-2 mediate induction of acid sphingomyelinase during monocytic differentiation. J. Lipid Res. 40: 870-880 [Abstract] [Full Text]  
  • Dorflinger, U., Pscherer, A., Moser, M., Rummele, P., Schule, R., Buettner, R. (1999). Activation of Somatostatin Receptor II Expression by Transcription Factors MIBP1 and SEF-2 in the Murine Brain. Mol. Cell. Biol. 19: 3736-3747 [Abstract] [Full Text]  
  • Allgayer, H., Wang, H., Wang, Y., Heiss, M. M., Bauer, R., Nyormoi, O., Boyd, D. (1999). Transactivation of the Urokinase-type Plasminogen Activator Receptor Gene through a Novel Promoter Motif Bound with an Activator Protein-2alpha -related Factor. J. Biol. Chem. 274: 4702-4714 [Abstract] [Full Text]  
  • Imhof, A., Schuierer, M., Werner, O., Moser, M., Roth, C., Bauer, R., Buettner, R. (1999). Transcriptional Regulation of the AP-2alpha Promoter by BTEB-1 and AP-2rep, a Novel wt-1/egr-Related Zinc Finger Repressor. Mol. Cell. Biol. 19: 194-204 [Abstract] [Full Text]  
  • Kannan, P., Tainsky, M. A. (1999). Coactivator PC4 Mediates AP-2 Transcriptional Activity and Suppresses ras-Induced Transformation Dependent on AP-2 Transcriptional Interference. Mol. Cell. Biol. 19: 899-908 [Abstract] [Full Text]  
  • Ries, S., Büchler, C., Langmann, T., Fehringer, P., Aslanidis, C., Schmitz, G. (1998). Transcriptional regulation of lysosomal acid lipase in differentiating monocytes is mediated by transcription factors Sp1 and AP-2. J. Lipid Res. 39: 2125-2134 [Abstract] [Full Text]  
  • Jean, D., Gershenwald, J. E., Huang, S., Luca, M., Hudson, M. J., Tainsky, M. A., Bar-Eli, M. (1998). Loss of AP-2 Results in Up-regulation of MCAM/MUC18 and an Increase in Tumor Growth and Metastasis of Human Melanoma Cells. J. Biol. Chem. 273: 16501-16508 [Abstract] [Full Text]  
  • Leppa, S., Pirkkala, L., Saarento, H., Sarge, K. D., Sistonen, L. (1997). Overexpression of HSF2-beta Inhibits Hemin-induced Heat Shock Gene Expression and Erythroid Differentiation in K562 Cells. J. Biol. Chem. 272: 15293-15298 [Abstract] [Full Text]  
  • Lee, B. S., Krits, I., Crane-Zelkovic, M. K., Gluck, S. L. (1997). A Novel Transcription Factor Regulates Expression of the Vacuolar H+-ATPase B2 Subunit through AP-2 Sites during Monocytic Differentiation. J. Biol. Chem. 272: 174-181 [Abstract] [Full Text]  
  • LaPres, J. J., Hudson, L. G. (1996). Identification of a Functional Determinant of Differentiation-dependent Expression in the Involucrin Gene. J. Biol. Chem. 271: 23154-23160 [Abstract] [Full Text]  
  • Bosserhoff, A. K., Hein, Rüd., Bogdahn, U., Buettner, R. (1996). Structure and Promoter Analysis of the Gene Encoding the Human Melanoma-inhibiting Protein MIA. J. Biol. Chem. 271: 490-495 [Abstract] [Full Text]  
  • Duan, C., Clemmons, D. R. (1995). Transcription Factor AP-2 Regulates Human Insulin-like Growth Factor Binding Protein-5 Gene Expression. J. Biol. Chem. 270: 24844-24851 [Abstract] [Full Text]  
  • Moser, M, Imhof, A, Pscherer, A, Bauer, R, Amselgruber, W, Sinowatz, F, Hofstadter, F, Schule, R, Buettner, R (1995). Cloning and characterization of a second AP-2 transcription factor: AP-2 beta. Development 121: 2779-2788 [Abstract]  
  • Byrne, C., Tainsky, M., Fuchs, E. (1994). Programming gene expression in developing epidermis. Development 120: 2369-2383 [Abstract]  
  • Kannan, P, Buettner, R, Chiao, P J, Yim, S O, Sarkiss, M, Tainsky, M A (1994). N-ras oncogene causes AP-2 transcriptional self-interference, which leads to transformation.. Genes Dev. 8: 1258-1269 [Abstract]  
  • Wankhade, S., Yu, Y., Weinberg, J., Tainsky, M. A., Kannan, P. (2000). Characterization of the Activation Domains of AP-2 Family Transcription Factors. J. Biol. Chem. 275: 29701-29708 [Abstract] [Full Text]  
  • Biederer, C. H., Ries, S. J., Moser, M., Florio, M., Israel, M. A., McCormick, F., Buettner, R. (2000). The Basic Helix-Loop-Helix Transcription Factors Myogenin and Id2 Mediate Specific Induction of Caveolin-3 Gene Expression during Embryonic Development. J. Biol. Chem. 275: 26245-26251 [Abstract] [Full Text]  
  • Terzano, S., Flora, A., Clementi, F., Fornasari, D. (2000). The Minimal Promoter of the Human alpha 3 Nicotinic Receptor Subunit Gene. MOLECULAR AND FUNCTIONAL CHARACTERIZATION. J. Biol. Chem. 275: 41495-41503 [Abstract] [Full Text]  
  • Zhu, C.-H., Huang, Y., Oberley, L. W., Domann, F. E. (2001). A Family of AP-2 Proteins Down-regulate Manganese Superoxide Dismutase Expression. J. Biol. Chem. 276: 14407-14413 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»