The Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins

Landschulz, William; Johnson, Peter F.; McKnight, Steven L.

doi:10.1126/science.3289117

Cited by 3,377 publications

(2,039 citation statements)

References 49 publications

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“…LZ motifs mediate dimer formation via a coiled-coil arrangement of parallel ␣-helices, and are found in many eukaryotic transcription factors (Landschulz et al 1988). Although it is well established that many cell surface receptors mediate their action as dimers (Hebert and Bouvier 1998), it remains to be determined whether CD151 exists and functions as homodimer.…”

Section: Discussionmentioning

confidence: 99%

Tetraspan Protein CD151 A Common Target of Mood Stabilizing Drugs?

Hua

Green

Wong

et al. 2001

Neuropsychopharmacology

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The latency in onset of antimanic and mood stabilizing effects of lithium suggest that long-term neuronal adaptations mediated by changes in gene expression may be important to the therapeutic action of lithium treatment. Using differential display-polymerase chain reaction, several novel, hitherto unexpected lithium-regulated genes have been isolated, all of which would not have beenAlthough lithium is widely used in the treatment of acute mania and the prophylaxis for bipolar affective disorder, the cellular and molecular mechanisms underlying its therapeutic action remain unclear. However, significant progress has been made over the past decade with cumulative evidence indicating that modulation of postreceptor signaling mechanisms in critical regions of the brain may be essential to the mood stabilizing properties of this agent (reviewed in Jope 1999;Li et al. 2000;Manji and Lenox 1999).Many signal transduction cascades are known to induce long-term cellular responses through regulation of gene transcription. Moreover, the delayed onset of therapeutic action of lithium has led to the hypothesis that regulation of gene expression may be important for its mood stabilizing effects (Jope 1999;Li et al. 2000). In line with this hypothesis, several studies have demonstrated that chronic lithium treatment alters the expression of an array of genes, including G protein ␣ -subunits, adenylyl cyclase subtypes, neuropeptides (reviewed in Jope 1999;Li et al. 2000;Manji and Lenox 1999) NO . 5 et al. 2000). The modulatory effects of lithium on gene expression have been suggested to be mediated, at least in part, through the cAMP response element binding protein (CREB) or activator protein-1 (AP-1) transcriptional factor pathway (Ozaki and Chuang 1997;Asghari et al. 1998;Yuan et al. 1998). It is thus conceivable that other genes containing the consensus sequences for these transcription factors in their promoter region may also be the potential targets of lithium. Therefore, the identification of other lithium-regulated genes is important in better understanding the spectrum of cellular and molecular mechanisms that contribute to the therapeutic and/or side effects of this drug.Using differential display-polymerase chain reaction (ddPCR), several novel lithium-regulated genes have been identified that would not otherwise have been considered using a candidate gene approach. These novel lithium-regulated targets included 2 Ј , 3 Ј -cyclic nucleotide 3 Ј -phosphodiesterase type II (Wang and Young 1996), polyomavirus enhancer-binding protein 2 ␤ (Chen et al. 1999), nitrogen permease regulator 2 (Wang et al. 1999), aldolase A (Hua et al. 2000, and diphosphoinositol polyphosphate phosphohydrolase II (Hua et al. 2001). Unexpectedly, during the course of experiments amplifying the 5 Ј end of a putative lithium-regulated ddPCR fragment, we isolated another cDNA clone, a homolog of human/mouse transmembrane-4-superfamily (TM4SF) protein, CD151. The transcript levels of CD151 were significantly decreased in the rat frontal corte...

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Section: Discussionmentioning

confidence: 99%

Tetraspan Protein CD151 A Common Target of Mood Stabilizing Drugs?

Hua

Green

Wong

et al. 2001

Neuropsychopharmacology

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“…These genes encode components of the AP1 transcription factor formed by homo-or hetero-dimerization of the Jun and Fos proteins. Dimerization occurs through a leucine-repeat located in the highly conserved C-terminal part of the Jun proteins or in an internal position in the Fos proteins (Landschulz et al, 1988;Sassone-Corsi et al, 1988a). As the Fos proteins do not form dimers among themselves, AP1 is a set of low a nity Jun/Jun and high a nity Jun/Fos dimers (Nakabeppu et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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The Ras proteins play a central role in regulating cell growth and their mutation can lead to abnormal proliferation. To analyse the potential link betwen AP1 activity, encoded by members of the jun and fos gene families, and Ras-mediated cellular transformation, we have studied several NIH3T3 clones which overexpress the Ha-Ras or Ki-Ras oncogenes. These transformed ®broblasts accumulated higher levels of cJun, JunB, Fra1 and Fra2 proteins relative to their normal counterparts. They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers. Following serum stimulation of Ras clones, the elevated levels of cJun and Fra1 remained steady, while the induction of JunB and Fra2 was partially attenuated. Moreover, deregulated Ras signaling resulted in a complete loss of the serum inducibility of cFos and FosB. Ectopic co-expression of cJun and Fra1 in NIH3T3 ®broblasts led to a transformed phenotype, attenuation of cFos serum inducibility, increased AP1 activity and Cyclin D1 accumulation, all characteristics of oncogenic Ras expressing cells. These results demonstrate that cJun and Fra1 are crucial mediators of the Ras-transformation process.

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“…Members of the leucine zipper class of proteins include the AP-1 family (Vogt & BOS, 1990); the yeast transactivator, GCN4 (Hope & Struhl, 1986; the CAAT box binding transcription factor, C/EBP (Landschulz et al, 1988); and the CREWATF family of proteins (Hai et al, 1989). The leucine zipper proteins bind to their target DNA as dimers (Kouzarides & Ziff, 1988;Landschulz et al, 1988).…”

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confidence: 99%

Bacterial expression and characterization of the CREB bZip module: Circular dichroism and 2D ¹H‐NMR studies

et al. 1993

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In this paper we describe the expression and purification from bacteria of the recombinant basic leucine zipper (bZip) domain of the cAMP response element binding protein, CREB327. The bZip peptide, CREB259–327, purified to near homogeneity, maintains the sequence‐specific CRE site recognition demonstrated by in vitro competition assays. Alkylation of the three cysteine residues of CREB259–327 was employed to prevent aggregation of the peptide due to cysteine oxidation. The Kd of the purified native and modified CREB259–327 for the CRE site was determined by gel retardation assays to be on the order of 10−7 M. We employed CD spectroscopy to study the folding properties of the native and modified CREB259–327. The CD analyses of the native/modified CREB259–327 peptide demonstrated a 20% increase in the α‐helical content upon binding to the cAMP response‐element. Only a 5% increase in the α‐helical content of CREB259–327 is observed upon binding to the AP‐1 site. This observation contrasts with CREB from the GCN4 protein (Weiss, M.A., et al., 1990, Nature 347, 575–578). In addition, the two‐dimensional (2D) 1H‐NMR studies of the bZip CREB peptide further support the distinct features of the CREB protein, in comparison to GCN4. Analysis by CD and 2D NMR of the dimerization domain of CREB suggests that the distinct DNA binding characteristics of CREB reside in the basic portion of the bZip module.

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The Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins

Cited by 3,377 publications

References 49 publications

Tetraspan Protein CD151 A Common Target of Mood Stabilizing Drugs?

Tetraspan Protein CD151 A Common Target of Mood Stabilizing Drugs?

Transformation by ras modifies AP1 composition and activity

Bacterial expression and characterization of the CREB bZip module: Circular dichroism and 2D ¹H‐NMR studies

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The Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins

Cited by 3,377 publications

References 49 publications

Tetraspan Protein CD151 A Common Target of Mood Stabilizing Drugs?

Tetraspan Protein CD151 A Common Target of Mood Stabilizing Drugs?

Transformation by ras modifies AP1 composition and activity

Bacterial expression and characterization of the CREB bZip module: Circular dichroism and 2D 1H‐NMR studies

Contact Info

Product

Resources

About

Bacterial expression and characterization of the CREB bZip module: Circular dichroism and 2D ¹H‐NMR studies