Disease relevance of Luzp1

• Fusion genes were constructed which produce chimeric proteins containing leucine zipper domains from several proteins fused either to the DNA-binding domain of the Saccharomyces cerevisiae GAL4 protein or to the transcriptional activation domain of the herpes simplex virus VP16 protein [1].
• The prolonged expression of the leucine zipper fos/jun immediate early genes (IEG) has been correlated with neuronal death after cerebral ischemia [2].
• Although previous work has shown that the hepatitis B virus X protein (pX) stabilizes complexes between basic region leucine zipper (bZIP) proteins and target DNA, the relationship between enhanced binding and transcriptional activation has not been established [3].
• In response to portal hypertension induced by PV ligature, abundance of MYPT1 in PV and MA1 was significantly reduced and switched to the LZ-positive isoform [4].
• The possible inhibitory role of the leucine-zipper DNA binding protein c-fos in the regulation of hepatic gene expression after sepsis [5].

High impact information on Luzp1

• The recovered full-length cDNA encodes a 48 kDa protein, NEMO (NF-kappaB Essential MOdulator), which contains a putative leucine zipper motif [6].
• These two proteins share the 145 C-terminal amino acids that contain the basic DNA-binding domain and the leucine zipper dimerization helix [7].
• This family is characterized by leucine zipper domains compatible with that of the CCAAT/enhancer binding protein (C/EBP) [8].
• It is shown here that cGKIalpha is targeted to the smooth muscle cell contractile apparatus by a leucine zipper interaction with the myosin-binding subunit (MBS) of myosin phosphatase [9].
• A basic region of c-Myc is structurally related to the basic motifs of helix-loop-helix (HLH) and leucine zipper proteins, which provide sequence-specific DNA binding function [10].

Biological context of Luzp1

• In addition to three leucine zipper motifs located at the NH2 terminus, there are three nuclear localization signals and a large number of putative Ser/Thr phosphorylation sites [11].
• cDNA clones encoding a novel protein (LUZP) with three leucine zipper motifs were first identified from a murine bone marrow cDNA library [11].
• Comparative mapping data suggest that the human homolog of Luzp will map to human chromosome 1p36 [11].
• Interspecific backcross analyses have mapped Luzp to mouse chromosome 4 in proximity to Gpcr14 [11].
• The arrangement of these related amino acid sequences led to the prediction of a new structural motif, termed the "leucine zipper," that plays a role in facilitating sequence-specific interaction between protein and DNA [12].

Anatomical context of Luzp1

• Previously, we identified the basic leucine zipper transcription factor CCAAT/enhancer-binding protein beta (C/ EBPbeta) as an inhibitor of insulin gene transcription in pancreatic beta cells and showed that the expression of C/EBPbeta is upregulated in insulinoma-derived beta cell lines by sustained high glucose concentrations [13].
• An RNA polymerase II complex containing all essential initiation factors binds to the activation domain of PAR leucine zipper transcription factor thyroid embryonic factor [14].
• Nup107 is a novel nuclear pore complex protein that contains a leucine zipper [15].
• 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 [16].
• The functional contributions of individual periods were studied in mutants in which periods 2-6 were individually deleted from rat striated muscle alphaalpha-tropomyosin or replaced with a leucine zipper sequence [17].

Associations of Luzp1 with chemical compounds

• Directed mutagenesis of the cFos protein reveals that a leucine repeat structure is required for binding to cJun, in a manner consistent with the proposed function of the "leucine zipper." A novel domain adjacent to, but distinct from, the leucine repeat of cFos is required for DNA binding by cFos-cJun heterodimers [18].
• Every member also bears a conserved cysteine residue at or near the carboxyl terminus, immediately following the leucine zipper, that at least in vitro allows efficient disulfide cross-linking between paired zipper helices [19].
• A control mutant of dMax that contains a proline residue in the leucine-zipper region was unable to bind to N-Myc and did not revert the N-Myc-induced changes in cellular gene expression [20].
• Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering [21].
• However, the SREBPs are unique basic-helix-loop-helix leucine zipper proteins that not only bind to a subset of E-boxes but also to the direct repeat SRE-1 element of the low density lipoprotein receptor promoter as well as to variant sites present in the promoters for key enzymes of both cholesterol and fatty acid biosynthesis [22].

Regulatory relationships of Luzp1

• The overexpression of the mutant of the EVH1 domain or deletion of the extreme C-terminal leucine zipper motif markedly suppressed the synaptic localization of endogenous shank but not PSD-95 or GKAP [23].

Other interactions of Luzp1

• The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45 were also critical for these events [23].
• Computer analyses of the structure of the encoded Odf2 protein revealed an overall alpha-helical structure with two regions identical to the dimerization region of the leucine zipper motif [24].
• Vesl-2 (354 amino acids) was highly related to Vesl-1L in that both contain EVH1- and PDZ-like domains at the N terminus (86% conservation) and an MCC (mutated in colorectal cancer)-like domain and a leucine zipper at the C terminus [25].
• The c-Myc proto-oncogene is a basic helix-loop-helix leucine zipper (b/HLH/LZ) protein that participates in cellular growth and differentiation [26].
• Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver [27].

Analytical, diagnostic and therapeutic context of Luzp1

• Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif [28].
• The sequence analysis indicates that the novel protein, designated CELF, has a significant homology to C/EBP gene family proteins in the carboxyl-terminal part containing the basic region and the leucine zipper motif [29].
• The thermal stabilities of three wild-type muscle alpha-TMs and nine chimeras, in which the second and/or sixth or ninth coding exons of one alpha-TM cDNA were replaced with exons from other alpha-TM cDNAs, with a sequence encoding the GCN4 leucine zipper or a random coil sequence, have been obtained using circular dichroism spectroscopy [30].
• PKN, a novel protein kinase with a catalytic domain homologous to that of the protein kinase C (PKC) family and unique N-terminal leucine-zipper-like sequences, was identified by molecular cloning from a human hippocampus cDNA library [Mukai and Ono (1994) Biochem. Biophys. Res. Commun. 199, 897-904] [31].
• Synthetic model peptides corresponding to the proposed leucine zipper-like coiled-coil regions of proBNP, proANP and their related N-terminal peptides were shown to be sufficient to induce oligomerisation when assessed on size exclusion HPLC [32].

References