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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
MeSH Review

Leucine Zippers

 
 
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Disease relevance of Leucine Zippers

  • The product of the EBV BZLF1 early gene, EB1, a member of the basic leucine-zipper family of transcription factors, interacts with both viral and cellular promoters and transcription factors, modulating the reactivation of latent EBV infection [1].
  • Recently, a novel viral protein named HTLV-1 basic leucine-zipper factor, HBZ, has been shown to interact with c-Jun and repress c-Jun-mediated transcription by abrogating its DNA-binding activity [2].
  • As the first step toward the synthesis of a basic region-retro leucine zipper HIV enhancer-binding fusion protein, we have now prepared the retro version of the leucine zipper (r-LZ35) and performed initial physicochemical characterization [3].
 

High impact information on Leucine Zippers

  • Embedded within these leucine-zipper layers is an ionic layer consisting of an arginine and three glutamine residues contributed from each of the four alpha-helices [4].
  • The basic/leucine zipper (bZip) transcription factor, CREB, binds to the CRE element (TGANNTCA) [5].
  • We show that a 32-residue alpha-helical peptide based on the leucine-zipper domain of the yeast transcription factor GCN4 can act autocatalytically in templating its own synthesis by accelerating the thioester-promoted amide-bond condensation of 15- and 17-residue fragments in neutral, dilute aqueous solutions [6].
  • The folding free energy of the leucine-zipper dimerization domain was harnessed to twist the dimer interface of the receptor, which markedly affected the extent of CheA activation [7].
  • Here, it is shown that BRCA1 interacts with Jun proteins via a coiled-coil motif in AD1 and the basic leucine zipper (bZIP) region of the Jun proteins [8].
 

Biological context of Leucine Zippers

 

Anatomical context of Leucine Zippers

  • Mitf, a basic helix-loop-helix leucine zipper (b-HLH-LZ) transcription factor associated with the onset and maintenance of pigmentation, identifies the retinal pigmented epithelium during eye development [14].
 

Associations of Leucine Zippers with chemical compounds

  • The sequence in the 22-kD zein gene promoter that is recognized by O2 is similar to the target site recognized by other "basic/leucine zipper" (bZIP) proteins in that it contains an ACGT core that is necessary for DNA binding [15].
  • To define the basis for structural heterogeneity, we determined the high resolution X-ray crystal structures of a single GCN4 leucine-zipper mutant (Asn 16 to aminobutyric acid) in both dimeric and trimeric coiled-coil conformations [16].
  • Auxin-induced stress potentiates trans-activation by a conserved plant basic/leucine-zipper factor [17].
  • C1 spans the sequences missing in AMV v-myb while C2, which contains the leucine-zipper motif is specifically absent in the E26 v-myb in addition to C1 [18].
  • The proteins encoded by the Gpa2 and the Rx1 genes share an overall homology of over 88% (amino-acid identity) and belong to the leucine-zipper, nucleotide-binding site, leucine-rich repeat (LZ-NBS-LRR)-containing class of plant resistance genes [19].
 

Gene context of Leucine Zippers

  • Deletion analysis of the various functional domains of ATF6 indicated that the interaction was through its leucine-zipper domain [20].
  • Cbf1 belongs to the basic helix-loop-helix DNA-binding protein family while Met4 and Met28 are two basic leucine zipper (bZIP) factors [21].
  • The basic helix-loop-helix leucine zipper (bHLHZIP) protein TFE3 and Smad3 synergistically activate transcription of the plasminogen activator inhibitor-1 (PAI-1) as well as other genes [22].
  • The crystal structure of the heterodimer formed by the basic leucine zipper (bZIP) domains of activating transcription factor-4 (ATF4) and CCAAT box/enhancer-binding protein beta (C/EBP beta), from two different bZIP transcription factor families, has been determined and refined to 2.6 A [23].
  • Ire1p regulates synthesis of the basic leucine-zipper (bZIP)-containing transcription factor Hac1p by controlling splicing of HAC1 mRNA [24].
 

Analytical, diagnostic and therapeutic context of Leucine Zippers

  • Individual glucocorticoid (GC) sensitivity was determined by measuring the effects of several clinically used GCs on transactivation of the GC-induced leucine zipper (GILZ) gene and on transrepression of the IL-2 gene using quantitative real-time PCR [25].

References

  1. Ubinuclein, a novel nuclear protein interacting with cellular and viral transcription factors. Aho, S., Buisson, M., Pajunen, T., Ryoo, Y.W., Giot, J.F., Gruffat, H., Sergeant, A., Uitto, J. J. Cell Biol. (2000) [Pubmed]
  2. HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein. Matsumoto, J., Ohshima, T., Isono, O., Shimotohno, K. Oncogene (2005) [Pubmed]
  3. Synthesis, physicochemical characterization, and crystallization of a putative retro-coiled coil. Liu, N., Deillon, C., Klauser, S., Gutte, B., Thomas, R.M. Protein Sci. (1998) [Pubmed]
  4. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Sutton, R.B., Fasshauer, D., Jahn, R., Brunger, A.T. Nature (1998) [Pubmed]
  5. Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB. Barton, K., Muthusamy, N., Chanyangam, M., Fischer, C., Clendenin, C., Leiden, J.M. Nature (1996) [Pubmed]
  6. A self-replicating peptide. Lee, D.H., Granja, J.R., Martinez, J.A., Severin, K., Ghadri, M.R. Nature (1996) [Pubmed]
  7. Imitation of Escherichia coli aspartate receptor signaling in engineered dimers of the cytoplasmic domain. Cochran, A.G., Kim, P.S. Science (1996) [Pubmed]
  8. JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction. Hu, Y.F., Li, R. Genes Dev. (2002) [Pubmed]
  9. SIN3-dependent transcriptional repression by interaction with the Mad1 DNA-binding protein. Kasten, M.M., Ayer, D.E., Stillman, D.J. Mol. Cell. Biol. (1996) [Pubmed]
  10. DNA binding specificity of the wheat bZIP protein EmBP-1. Niu, X., Guiltinan, M.J. Nucleic Acids Res. (1994) [Pubmed]
  11. Identification of Gasz, an evolutionarily conserved gene expressed exclusively in germ cells and encoding a protein with four ankyrin repeats, a sterile-alpha motif, and a basic leucine zipper. Yan, W., Rajkovic, A., Viveiros, M.M., Burns, K.H., Eppig, J.J., Matzuk, M.M. Mol. Endocrinol. (2002) [Pubmed]
  12. The intrinsic ability of AFAP-110 to alter actin filament integrity is linked with its ability to also activate cellular tyrosine kinases. Baisden, J.M., Gatesman, A.S., Cherezova, L., Jiang, B.H., Flynn, D.C. Oncogene (2001) [Pubmed]
  13. Visualization of protein interactions in living plant cells using bimolecular fluorescence complementation. Walter, M., Chaban, C., Schütze, K., Batistic, O., Weckermann, K., Näke, C., Blazevic, D., Grefen, C., Schumacher, K., Oecking, C., Harter, K., Kudla, J. Plant J. (2004) [Pubmed]
  14. Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins. Planque, N., Leconte, L., Coquelle, F.M., Martin, P., Saule, S. J. Biol. Chem. (2001) [Pubmed]
  15. Opaque-2 is a transcriptional activator that recognizes a specific target site in 22-kD zein genes. Schmidt, R.J., Ketudat, M., Aukerman, M.J., Hoschek, G. Plant Cell (1992) [Pubmed]
  16. Crystal structures of a single coiled-coil peptide in two oligomeric states reveal the basis for structural polymorphism. Gonzalez, L., Brown, R.A., Richardson, D., Alber, T. Nat. Struct. Biol. (1996) [Pubmed]
  17. Auxin-induced stress potentiates trans-activation by a conserved plant basic/leucine-zipper factor. Pascuzzi, P., Hamilton, D., Bodily, K., Arias, J. J. Biol. Chem. (1998) [Pubmed]
  18. The carboxy-terminal domain of c-Myb activates reporter gene expression in yeast. Seneca, S., Punyammalee, B., Sureau, A., Perbal, B., Dvorák, M., Crabeel, M. Oncogene (1993) [Pubmed]
  19. Homologues of a single resistance-gene cluster in potato confer resistance to distinct pathogens: a virus and a nematode. van der Vossen, E.A., van der Voort, J.N., Kanyuka, K., Bendahmane, A., Sandbrink, H., Baulcombe, D.C., Bakker, J., Stiekema, W.J., Klein-Lankhorst, R.M. Plant J. (2000) [Pubmed]
  20. ATF6 modulates SREBP2-mediated lipogenesis. Zeng, L., Lu, M., Mori, K., Luo, S., Lee, A.S., Zhu, Y., Shyy, J.Y. EMBO J. (2004) [Pubmed]
  21. Assembly of a bZIP-bHLH transcription activation complex: formation of the yeast Cbf1-Met4-Met28 complex is regulated through Met28 stimulation of Cbf1 DNA binding. Kuras, L., Barbey, R., Thomas, D. EMBO J. (1997) [Pubmed]
  22. Both Max and TFE3 cooperate with Smad proteins to bind the plasminogen activator inhibitor-1 promoter, but they have opposite effects on transcriptional activity. Grinberg, A.V., Kerppola, T. J. Biol. Chem. (2003) [Pubmed]
  23. Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA. Podust, L.M., Krezel, A.M., Kim, Y. J. Biol. Chem. (2001) [Pubmed]
  24. IRE1- and HAC1-independent transcriptional regulation in the unfolded protein response of yeast. Schröder, M., Clark, R., Kaufman, R.J. Mol. Microbiol. (2003) [Pubmed]
  25. Differential regulation of synthetic glucocorticoids on gene expression levels of glucocorticoid-induced leucine zipper and interleukin-2. Smit, P., Russcher, H., de Jong, F.H., Brinkmann, A.O., Lamberts, S.W., Koper, J.W. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
 
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