A 30-amino-acid segment of C/EBP, a newly discovered enhancer binding protein, shares notable sequence similarity with a segment of the cellular Myc transforming protein. Display of these respective amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The periodic array of at least four leucines was also noted in the sequences of the Fos and Jun transforming proteins, as well as that of the yeast gene regulatory protein, GCN4. The polypeptide segments containing these periodic arrays of leucine residues are proposed to exist in an alpha-helical conformation, and the leucine side chains extending from one alpha helix interdigitate with those displayed from a similar alpha helix of a second polypeptide, facilitating dimerization. This hypothetical structure is referred to as the "leucine zipper," and it may represent a characteristic property of a new category of DNA binding proteins.

https://science.sciencemag.org/content/sci/240/4860/1759.full.pdf

The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins

The cloning of genes encoding mammalian DNA binding transcription factors for RNA polymerase II has provided the opportunity to analyze the structure and function of these proteins. This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors. The mechanisms by which these factors may activate transcriptional initiation and by which they may be regulated to achieve differential gene expression are also discussed.

https://science.sciencemag.org/content/sci/245/4916/371.full.pdf

Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins

A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins

In cells that do not express immunoglobulin kappa light chain genes, the kappa enhancer binding protein NF-kappa B is found in cytosolic fractions and exhibits DNA binding activity only in the presence of a dissociating agent such as sodium deoxycholate. The dependence on deoxycholate is shown to result from association of NF-kappa B with a 60- to 70-kilodalton inhibitory protein (I kappa B). The fractionated inhibitor can inactivate NF-kappa B from various sources--including the nuclei of phorbol ester-treated cells--in a specific, saturable, and reversible manner. The cytoplasmic localization of the complex of NF-kappa B and I kappa B was supported by enucleation experiments. An active phorbol ester must therefore, presumably by activation of protein kinase C, cause dissociation of a cytoplasmic complex of NF-kappa B and I kappa B by modifying I kappa B. this releases active NF-kappa B which can translocate into the nucleus to activate target enhancers. The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor.

https://science.sciencemag.org/content/sci/242/4878/540.full.pdf

I kappa B: a specific inhibitor of the NF-kappa B transcription factor.

Nucleic acid molecules capable of hybridizing under stringent conditions to the nucleotide sequence residing between positions 1 and 453 of the max cDNAs shown in Figure 2, or to the nucleotide sequence reisiding between positions 148 and 810 of the mad cDNAs shown in Figure 14. The Max polypeptide when associated with the Myc or Mad polypeptide is capable of binding to nucleotide sequences containing CACGTG.

https://science.sciencemag.org/content/sci/251/4998/1211.full.pdf

Max: a helix-loop-helix zipper protein that forms a sequence-specific dna-binding complex with myc and mad

https://cdr.lib.unc.edu/downloads/n296x153f

Molecular cloning of an enhancer binding protein:Isolation by screening of an expression library with a recognition site DNA

https://cdr.lib.unc.edu/downloads/rv042w24b

Human CCAAT-binding proteins have heterologous subunits

A sequence centered 166 nucleotides upstream of the mouse H-2Kb class I major histocompatibility gene binds a nuclear factor, H2TF1, found in many cell types. Previous studies have shown that binding of H2TF1 to this sequence stimulates class I gene expression. Furthermore, this factor binds a similar sequence in the 72-base-pair repeat enhancer element of simian virus 40. We show here that NF-kappa B, an inducible B-cell-specific factor that binds the kappa immunoglobulin light chain gene enhancer, also binds the H2TF1 regulatory sequence. Methylation-interference experiments demonstrate that NF-kappa B closely interacts with six of the eight symmetrically positioned guanines that contact H2TF1. These experiments suggest that NF-kappa B may play a role in class I major histocompatibility gene expression and that H2TF1 and NF-kappa B may be related DNA-binding proteins.

https://www.pnas.org/content/pnas/85/3/723.full.pdf

Two transcription factors, NF-kappa B and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter.

The myc gene seems to have a causal role in tumour formation in man, mouse and avian systems1–3. The myc gene product has been localized to the nucleus4,5, suggesting that it may be involved in the regulation of gene expression. The level of expression of the mammalian heat shock protein 70 (HSP70) gene is elevated in several tumour cell lines6, implying that a cellular function expressed in these tumour lines can stimulate HSP70 production. We report here that the gene product of a rearranged mouse c-myc gene is capable of stimulating expression of chimaeric genes containing a Drosophila hsp70 promoter region and 5′-flanking sequences. This stimulation is dependent on sequences located more than 200 bases 5′ of the normal start of hsp70 transcription.

Albert S. Baldwin

Papers

Molecular cloning of an enhancer binding protein:Isolation by screening of an expression library with a recognition site DNA

Human CCAAT-binding proteins have heterologous subunits

Two transcription factors, NF-kappa B and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter.

Regulation of heat shock protein 70 gene expression by c-myc.

Transcription Control by Oncogenes