scholarly journals Molecular Characterization of abLIM, a Novel Actin-binding and Double Zinc Finger Protein

1997 ◽  
Vol 138 (3) ◽  
pp. 575-588 ◽  
Author(s):  
Dorothy J. Roof ◽  
Annmarie Hayes ◽  
Michael Adamian ◽  
Athar H. Chishti ◽  
Tiansen Li
Keyword(s):  
Zinc Finger ◽  
Intracellular Signaling ◽  
Time Course ◽  
Zinc Finger Protein ◽  
Binding Capacity ◽  
Consensus Sequence ◽  
Developmental Expression ◽  
Actin Binding ◽  
General Role ◽  
Outer Segments

Molecules that couple the actin-based cytoskeleton to intracellular signaling pathways are central to the processes of cellular morphogenesis and differentiation. We have characterized a novel protein, the actin-binding LIM (abLIM) protein, which could mediate such interactions between actin filaments and cytoplasmic targets. abLIM protein consists of a COOH-terminal cytoskeletal domain that is fused to an NH2-terminal domain consisting of four double zinc finger motifs. The cytoskeletal domain is ∼50% identical to erythrocyte dematin, an actin-bundling protein of the red cell membrane skeleton, while the zinc finger domains conform to the LIM motif consensus sequence. In vitro expression studies demonstrate that abLIM protein can bind to F-actin through the dematin-like domain. Transcripts corresponding to three distinct isoforms have a widespread tissue distribution. However, a polypeptide corresponding to the full-length isoform is found exclusively in the retina and is enriched in biochemical extracts of retinal rod inner segments. abLIM protein also undergoes extensive phosphorylation in light-adapted retinas in vivo, and its developmental expression in the retina coincides with the elaboration of photoreceptor inner and outer segments. Based on the composite primary structure of abLIM protein, actin-binding capacity, potential regulation via phosphorylation, and isoform expression pattern, we speculate that abLIM may play a general role in bridging the actin-based cytoskeleton with an array of potential LIM protein-binding partners. The developmental time course of abLIM expression in the retina suggests that the retina-specific isoform may have a specialized role in the development or elaboration of photoreceptor inner and outer segments.

scholarly journals A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter.

1995 ◽  
Vol 15 (6) ◽  
pp. 3179-3186 ◽  
Author(s):  
D D Duncan ◽  
A Stupakoff ◽  
S M Hedrick ◽  
K B Marcu ◽  
G Siu
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Consensus Sequence ◽  
Developmental Expression ◽  
Critical Element ◽  
Factor Binding ◽  
Functional Regions ◽  
Finger Protein ◽  
Myc Gene ◽  
Predominant Factor

The CD4 promoter plays an important role in the developmental control of CD4 transcription. In this report, we show that the minimal CD4 promoter has four factor binding sites, each of which is required for full function. Using biochemical and mutagenesis analyses, we determined that multiple nuclear factors bind to these independent sites. We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function. We also demonstrate that the Myc-associated zinc finger protein (MAZ) appears to be the predominant factor binding to one of these sites. This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene. We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene.

scholarly journals Structural Insights into c-Myc-interacting Zinc Finger Protein-1 (Miz-1) Delineate Domains Required for DNA Scanning and Sequence-specific Binding

2016 ◽  
Vol 292 (8) ◽  
pp. 3323-3340 ◽  
Author(s):  
Mikaël Bédard ◽  
Vincent Roy ◽  
Martin Montagne ◽  
Pierre Lavigne
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Dna Sequences ◽  
Zinc Finger Protein ◽  
Specific Binding ◽  
Consensus Sequence ◽  
Compact Structure ◽  
General Role ◽  
Finger Protein

c-Myc-interacting zinc finger protein-1 (Miz-1) is a poly-Cys2His2 zinc finger (ZF) transcriptional regulator of many cell cycle genes. A Miz-1 DNA sequence consensus has recently been identified and has also unveiled Miz-1 functions in other cellular processes, underscoring its importance in the cell. Miz-1 contains 13 ZFs, but it is unknown why Miz-1 has so many ZFs and whether they recognize and bind DNA sequences in a typical fashion. Here, we used NMR to deduce the role of Miz-1 ZFs 1–4 in detecting the Miz-1 consensus sequence and preventing nonspecific DNA binding. In the construct containing the first 4 ZFs, we observed that ZFs 3 and 4 form an unusual compact and stable structure that restricts their motions. Disruption of this compact structure by an electrostatically mismatched A86K mutation profoundly affected the DNA binding properties of the WT construct. On the one hand, Miz1–4WT was found to bind the Miz-1 DNA consensus sequence weakly and through ZFs 1–3 only. On the other hand, the four ZFs in the structurally destabilized Miz1–4A86K mutant bound to the DNA consensus with a 30-fold increase in affinity (100 nm). The formation of such a thermodynamically stable but nonspecific complex is expected to slow down the rate of DNA scanning by Miz-1 during the search for its consensus sequence. Interestingly, we found that the motif stabilizing the compact structure between ZFs 3 and 4 is conserved and enriched in other long poly-ZF proteins. As discussed in detail, our findings support a general role of compact inter-ZF structures in minimizing the formation of off-target DNA complexes.

Repeated CT elements bound by zinc finger proteins control the absolute and relative activities of the two principal human c-myc promoters

1993 ◽  
Vol 13 (9) ◽  
pp. 5710-5724
Author(s):  
E DesJardins ◽  
N Hay
Keyword(s):  
Zinc Finger ◽  
Tandem Repeats ◽  
Zinc Finger Protein ◽  
Consensus Sequence ◽  
Regulatory Region ◽  
Maximal Activity ◽  
Single Copy ◽  
Promoter Usage

Transcription of the human proto-oncogene c-myc is governed by two tandem principal promoters, termed P1 and P2. In general, the downstream promoter, P2, is predominant, which is in contrast to the promoter occlusion phenomenon usually observed in genes containing tandem promoters. A shift in human c-myc promoter usage has been observed in some tumor cells and in certain physiological conditions. However, the mechanisms that regulate promoter usage are not well understood. The present studies identify regulators which are required to promote transcription from both human c-myc promoters, P1 and P2, and have a role in determining their relative activities in vivo. A novel regulatory region located 101 bp upstream of P1 was characterized and contains five tandem repeats of the consensus sequence CCCTCCCC (CT element). The integrity of the region containing all five elements is required to promote transcription from P1 and for maximal activity from P2 in vivo. A single copy of this same element, designated CT-I2, also appears in an inverted orientation 53 bp upstream of the P2 transcription start site. This element has an inhibitory effect on P1 transcription and is required for P2 transcription. The transcription factor Sp1 was identified as the factor that binds specifically to the tandem CT elements upstream of P1 and to the CT-I2 element upstream of P2. In addition, the recently cloned zinc finger protein ZF87, or MAZ, was also able to bind these same elements in vitro. The five tandem CT elements can be functionally replaced by a heterologous enhancer that only in the absence of CT-I2 reverses the promoter usage, similar to what is observed in the translocated c-myc allele of Burkitt's lymphoma cells.

Restricted expression of a zinc finger protein in male germ cells

1994 ◽  
Vol 13 (2) ◽  
pp. 157-165 ◽  
Author(s):  
R Hosseini ◽  
P Marsh ◽  
J Pizzey ◽  
L Leonard ◽  
S Ruddy ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Germ Cells ◽  
Time Course ◽  
Zinc Finger Protein ◽  
Western Blots ◽  
Male Germ Cells ◽  
Thin Sections ◽  
Zinc Finger Protein Gene ◽  
Finger Protein ◽  
Time Course Study

ABSTRACT Zfp-37 is a zinc finger protein gene expressed in male germ cells. The cDNA detected two transcripts on Northern blots of testis RNA, with expression first detected at around day 19. To establish the pattern of expression of the protein we have raised antibodies to ZFP-37 and used them on thin sections of testis and on Western blots. On Western blots the antibody detected two proteins exclusively in testis extracts, confirming the previous mRNA expression data. A time-course study revealed that the larger of the two proteins appears at about day 22 but the smaller one is not detected until day 34. Analysis of the expression of these two proteins in purified germ cell preparations revealed that the smaller protein is only detectable in the elongating spermatids or residual bodies. Data from thin sections showed that most, but not all, of the protein recognized by the antibody is in the nucleus, a result further confirmed by Western blotting. These results are discussed in the light of the possible role of this protein in regulating spermatogenesis.

Developmental expression of the Zinc-finger protein in

1990 ◽  
Vol 14 ◽  
pp. 58
Author(s):  
F RIJLI ◽  
S DELUCCHINI ◽  
C IGNACCHITI ◽  
F GRANUCCI ◽  
G CILIBERTO ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Developmental Expression ◽  
Finger Protein

scholarly journals Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth

2018 ◽  
Vol 115 (16) ◽  
pp. E3808-E3816 ◽  
Author(s):  
Shady Younis ◽  
Wael Kamel ◽  
Tina Falkeborn ◽  
Hao Wang ◽  
Di Yu ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Nuclear Export ◽  
High Throughput Sequencing ◽  
Rna Binding ◽  
Semliki Forest Virus ◽  
Zinc Finger Protein ◽  
Binding Capacity ◽  
Binding Property ◽  
Nuclear Regions ◽  
Simplex Virus

The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A–cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.

scholarly journals Isolation and developmental expression of a rat cDNA encoding a cysteine-rich zinc finger protein

1994 ◽  
Vol 22 (24) ◽  
pp. 5477-5483 ◽  
Author(s):  
Colleen R. McLaughlin ◽  
Qing Tao ◽  
Mary E. Abood
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Developmental Expression ◽  
Finger Protein

scholarly journals Zinc Finger Transcription Factors Designed for Bispecific Coregulation of ErbB2 and ErbB3 Receptors: Insights into ErbB Receptor Biology

2005 ◽  
Vol 25 (20) ◽  
pp. 9082-9091 ◽  
Author(s):  
Caren V. Lund ◽  
Mikhail Popkov ◽  
Laurent Magnenat ◽  
Carlos F. Barbas
Keyword(s):  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Migration ◽  
Zinc Finger ◽  
Intracellular Signaling ◽  
Zinc Finger Protein ◽  
Mitogen Activated Protein Kinase ◽  
Erbb Receptors ◽  
Erbb Receptor ◽  
Receptor Biology

ABSTRACT Signaling through the ErbB family of tyrosine kinase receptors in normal and cancer-derived cell lines contributes to cell growth and differentiation. In this work, we altered the levels of ErbB2 and ErbB3 receptors, individually and in combination, by using 6-finger and 12-finger synthetic zinc finger protein artificial transcription factors (ATFs) in an epidermoid squamous cell carcinoma line, A431. We successfully designed 12-finger ATFs capable of coregulating ErbB3 and ICAM-1 or ErbB2 and ErbB3. With ATFs, the effects of changes in ErbB2 and ErbB3 receptor levels were evaluated by using cell proliferation, cell migration, and cell signaling assays. Cell proliferation was increased when ErbB2 and ErbB3 were both overexpressed. Cell migration on collagen was decreased when ErbB2 was down-regulated, yet migration on laminin was significantly increased with ErbB3 overexpression. ErbB2 and ErbB3 overexpression also stimulated the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. Our ATF approach has elucidated differences in ErbB receptor-mediated proliferation, migration, and intracellular signaling that cannot be explained merely by the presence or absence of particular ErbB receptors and emphasizes the dynamic nature of the ErbB signaling system. The transcription factor approach developed here provides a gene-economical route to the regulation of multiple genes and may be important for complex gene therapies.

Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence

Science ◽  
1990 ◽  
Vol 250 (4985) ◽  
pp. 1259-1262 ◽  
Author(s):  
F. Rauscher ◽  
J. Morris ◽  
O. Tournay ◽  
D. Cook ◽  
T Curran
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Wilms Tumor ◽  
Consensus Sequence ◽  
Finger Protein
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