Cubitus interruptus-independent transduction of the Hedgehog signal in Drosophila

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5509-5522 ◽  
Author(s):  
A. Gallet ◽  
C. Angelats ◽  
S. Kerridge ◽  
P.P. Therond
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Drosophila Embryo ◽  
Key Factors ◽  
Cubitus Interruptus ◽  
Finger Protein ◽  
Control Pattern ◽  
Hedgehog Signal

The Hedgehog (Hh) family of secreted proteins are key factors that control pattern formation in invertebrates and vertebrates. The manner in which Hh molecules regulate a target cell remains poorly understood. In the Drosophila embryo, Hh is produced in identical stripes of cells in the posterior compartment of each segment. From these cells a Hh signal acts in both anterior and posterior directions. In the anterior cells, the target genes wingless and patched are activated whereas posterior cells respond to Hh by expressing rhomboid and patched. Here, we have examined the role of the transcription factor Cubitus interruptus (Ci) in this process. So far, Ci has been thought to be the most downstream component of the Hh pathway capable of activating all Hh functions. However, our current study of a null ci allele, indicates that it is actually not required for all Hh functions. Whereas Hh and Ci are both required for patched expression, the target genes wingless and rhomboid have unequal requirements for Hh and Ci activity. Hh is required for the maintenance of wingless expression before embryonic stage 11 whereas Ci is necessary only later during stage 11. For rhomboid expression Hh is required positively whereas Ci exhibits negative input. These results indicate that factors other than Ci are necessary for Hh target gene regulation. We present evidence that the zinc-finger protein Teashirt is one candidate for this activity. We show that it is required positively for rhomboid expression and that Teashirt and Ci act in a partially redundant manner before stage 11 to maintain wingless expression in the trunk.

scholarly journals CHOP-Dependent Stress-Inducible Expression of a Novel Form of Carbonic Anhydrase VI

1999 ◽  
Vol 19 (1) ◽  
pp. 495-504 ◽  
Author(s):  
John Sok ◽  
Xiao-Zhong Wang ◽  
Nikoleta Batchvarova ◽  
Masahiko Kuroda ◽  
Heather Harding ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Target Gene ◽  
Target Genes ◽  
Direct Evidence ◽  
Nuclear Protein ◽  
Intracellular Form ◽  
Carbonic Anhydrase Vi ◽  
Responsive Element

ABSTRACT CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPβ dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducibleCA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VIexpression in c/ebpβ−/− cells by exogenous C/EBPβ and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

An anti-inflammatory role of A20 zinc finger protein during trauma combined with endotoxin challenge

2013 ◽  
Vol 185 (2) ◽  
pp. 717-725 ◽  
Author(s):  
Bo Liu ◽  
Dianming Jiang ◽  
Yunsheng Ou ◽  
Zhenming Hu ◽  
Jianxin Jiang ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Endotoxin Challenge ◽  
Finger Protein ◽  
Anti Inflammatory

scholarly journals Trans-activation of the human SOX3 promoter by MAZ in NT2/D1 cells

2008 ◽  
Vol 60 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Natasa Kovacevic-Grujicic ◽  
Kazunari Yokoyama ◽  
Milena Stevanovic
Keyword(s):  
Gene Expression ◽  
Neuronal Differentiation ◽  
Gene Transcription ◽  
Binding Sites ◽  
Promoter Activity ◽  
Zinc Finger Protein ◽  
Mobility Shift ◽  
Finger Protein ◽  
Sox3 Gene

In this study, we examine the role of three highly conserved putative binding sites for Myc-associated zinc finger protein (MAZ) in regulation of the human SOX3 gene expression. Electrophoretic mobility shift and supershift assays indicate that complexes formed at two out of three MAZ sites of the human SOX3 promoter involve ubiquitously expressed MAZ protein. Furthermore, in cotransfection experiments we demonstrate that MAZ acts as a positive regulator of SOX3 gene transcription in both undifferentiated and RA-differentiated NT2/D1 cells. Although MAZ increased both basal and RA-induced promoter activity, our results suggest that MAZ does not contribute to RA inducibility of the SOX3 promoter during neuronal differentiation of NT2/D1 cells.

scholarly journals The Cardiac Tissue-Restricted Homeobox Protein Csx/Nkx2.5 Physically Associates with the Zinc Finger Protein GATA4 and Cooperatively Activates Atrial Natriuretic Factor Gene Expression

1998 ◽  
Vol 18 (6) ◽  
pp. 3120-3129 ◽  
Author(s):  
Youngsook Lee ◽  
Tetsuo Shioi ◽  
Hideko Kasahara ◽  
Shawn M. Jobe ◽  
Russell J. Wiese ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zinc Finger ◽  
Protein Interaction ◽  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Target Gene ◽  
Cardiac Tissue ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Homeobox Protein

ABSTRACT Specification and differentiation of the cardiac muscle lineage appear to require a combinatorial network of many factors. The cardiac muscle-restricted homeobox protein Csx/Nkx2.5 (Csx) is expressed in the precardiac mesoderm as well as the embryonic and adult heart. Targeted disruption of Csx causes embryonic lethality due to abnormal heart morphogenesis. The zinc finger transcription factor GATA4 is also expressed in the heart and has been shown to be essential for heart tube formation. GATA4 is known to activate many cardiac tissue-restricted genes. In this study, we tested whether Csx and GATA4 physically associate and cooperatively activate transcription of a target gene. Coimmunoprecipitation experiments demonstrate that Csx and GATA4 associate intracellularly. Interestingly, in vitro protein-protein interaction studies indicate that helix III of the homeodomain of Csx is required to interact with GATA4 and that the carboxy-terminal zinc finger of GATA4 is necessary to associate with Csx. Both regions are known to directly contact the cognate DNA sequences. The promoter-enhancer region of the atrial natriuretic factor (ANF) contains several putative Csx binding sites and consensus GATA4 binding sites. Transient-transfection assays indicate that Csx can activate ANF reporter gene expression to the same extent that GATA4 does in a DNA binding site-dependent manner. Coexpression of Csx and GATA4 synergistically activates ANF reporter gene expression. Mutational analyses suggest that this synergy requires both factors to fully retain their transcriptional activities, including the cofactor binding activity. These results demonstrate the first example of homeoprotein and zinc finger protein interaction in vertebrates to cooperatively regulate target gene expression. Such synergistic interaction among tissue-restricted transcription factors may be an important mechanism to reinforce tissue-specific developmental pathways.

Abstract 5045: Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells.

2013 ◽  
Author(s):  
Raffaella Spina ◽  
Gessica Filocamo ◽  
Enrico Iaccino ◽  
Stefania Scicchitano ◽  
Michela Lupia ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Critical Role ◽  
Finger Protein ◽  
Tumorigenic Potential

Role of the Tristetraprolin (Zinc Finger Protein 36 Homolog) Gene in Cancer

2018 ◽  
Vol 28 (3) ◽  
pp. 217-221 ◽  
Author(s):  
Gaurav Gupta ◽  
Mary Bebawy ◽  
Terezinha de Jesus Andreoli Pinto ◽  
Dinesh Kumar Chellappan ◽  
Anurag Mishra ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Finger Protein

scholarly journals Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso

2012 ◽  
Vol 109 (38) ◽  
pp. 15229-15234 ◽  
Author(s):  
Bethany A. Buck-Koehntop ◽  
Robyn L. Stanfield ◽  
Damian C. Ekiert ◽  
Maria A. Martinez-Yamout ◽  
H. Jane Dyson ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Zinc Finger ◽  
Dna Sequences ◽  
Genome Stability ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Epigenetic Modification ◽  
Cpg Dinucleotides ◽  
Finger Protein ◽  
Dna Motif

Methylation of CpG dinucleotides in DNA is a common epigenetic modification in eukaryotes that plays a central role in maintenance of genome stability, gene silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional Cys2His2 zinc finger protein implicated in tumor-cell proliferation, binds to both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif (TCCTGCNA) and represses transcription by recruiting chromatin remodeling corepression machinery to target genes. Here we report structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated, sequence-specific DNA target (KBS) and with a symmetrically methylated DNA sequence derived from the promoter region of E-cadherin. Recognition of specific bases in the major groove of the core KBS and mCpG sites is accomplished through both classical and methyl CH···O hydrogen-bonding interactions with residues in the first two zinc fingers, whereas residues in the C-terminal extension following the third zinc finger bind in the opposing minor groove and are required for high-affinity binding. The C-terminal region is disordered in the free protein and adopts an ordered structure upon binding to DNA. The structures of these Kaiso complexes provide insights into the mechanism by which a zinc finger protein can recognize mCpG sites as well as a specific, nonmethylated regulatory DNA sequence.

The Regulation of Zinc Finger Proteins by Mirnas Enriched in ALL-Microvesicles

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1448-1448
Author(s):  
Huiyu Li ◽  
Xiaomei Chen ◽  
Wei Xiong ◽  
Fang Liu ◽  
Shiang Huang
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Expression Profiles ◽  
Zinc Fingers ◽  
Zinc Finger Proteins ◽  
Bioactive Molecules ◽  
Chromosomal Protein ◽  
Normal Peripheral Blood ◽  
Finger Protein

Abstract Abstract 1448 Microvesicles (MVs) are submicrometric membrane fragments and they can “hijack” membrane components and engulf cytoplasmic contents from their cellular origin. MVs are enriched in various bioactive molecules of their parental cells, such as proteins, DNA, mRNA and miRNAs. Microvesicles (MVs) released by leukemia cells constitute an important part of the leukemia microenvironment. As a cell-to-cell communication tool, MVs transfer microRNA (miRNA) between cells. MVs miRNAs may also provide an insight in the role of miRNAs playing in the underlying of pathophysiologic processes of various leukemia. We determined the miRNA expression profiles of ALL-derived MVs using Agilent miRNA microarray analysis. The five miRNAs obtained by microarray profiling were validated using real-time PCR. The putative target genes were predicted by bioformation software. We identified 182 and 166 dysregulated miRNAs in MVs derived from Nalm 6 cells and from Jurkat cells, respectively. Both up regulated (123/182 in Nalm 6-MVs and 114/166 in Jurkat- MVs) and down regulated (59/182 in Nalm 6-MVs and 52/166 in Jurkat- MVs) expressions were observed compared with MVs from normal peripheral blood the MVs normal control. When we analyzed those miRNA with bioinformatic tools (TargetScan), we found an interesting phenomenon that presence of 111 zinc fingers genes were regulated by 52 miRNAs, indicating that the ALL-microvesicles were enriched with miRNAs regulating zinc finger proteins. They encompassed zinc fingers and homeoboxes 2, zinc finger, ZZ-type containing 3, zinc finger, SWIM-type containing 1, zinc finger, RAN-binding domain containing 3, zinc finger, NFX1-type containing 1, zinc finger, MYM-type 4, zinc finger, FYVE domain containing 1 and their 5 subtypes; zinc finger, DHHC-type containing16, and other subtypes; zinc finger, CCHC domain containing 14 and 7A, zinc finger, BED-type containing 4; zinc finger protein, X-linked; zinc finger protein, multitype 2; zinc finger protein 81, and their 55 subtypes; zinc finger and SCAN domain containing 18, zinc finger and BTB domain containing 9. ALL-microvesicles were enriched with expression changes of distinct sets of miRNAs regulating zinc finger proteins. This provides clues that genes commonly function together. It is worth noting that 52 miRNA regulating above zinc finger protein genes were up-expressed, suggeting that miRNA regulating zinc fingers were active in ALL-MVs. Zinc finger proteins are important transcriptions in eukaryotes and play roles in regulating gene. Some members of the Zinc finger family have close relationaship with tumour. Zinc finger X-chromosomal protein (Zfx) is a protein that in humans is encoded by the ZFX gene. The level of Zfx expression correlates with aggressiveness and severity in many cancer types, including prostate cancer, breast cancer, gastric tumoural tissues, and leukemia. [1,2]. Zinc finger and homeoboxes 2 (ZHX2) was target gene of miRNA-1260. The role of miRNA are negatively regulated host gene expressions. ZHX2 inhibits HCC cell proliferation by preventing expression of Cyclins A and E, and reduces growth of xenograft tumors. Loss of nuclear ZHX2 might be an early step in the development of HCC[3]. In our study, the miRNA-1260 were 9 fold higher in ALL MVs. In leukeima microenvironment, ALL-MVs may transfer aberantly expressed miRNAs to their target cell lead to abnormally regulated the zinc finger proteins that may play roles in ALL. In this study, we demonstrated that ALL-microvesicles were enriched with expression changes of distinct sets of miRNAs regulating zinc finger proteins. Futhermore, Zinc fingers were active in ALL-MVs and commonly function together. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role of Gα12 and Gα13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

2007 ◽  
Vol 27 (17) ◽  
pp. 6195-6208 ◽  
Author(s):  
Min Kyung Cho ◽  
Won Dong Kim ◽  
Sung Hwan Ki ◽  
Jong-Ik Hwang ◽  
Sangdun Choi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Target Gene ◽  
Target Genes ◽  
Gene Knockout ◽  
Serine Phosphorylation ◽  
Related Factor ◽  
Dependent Signal ◽  
Extracellular Stimuli ◽  
Target Gene Induction

ABSTRACT Gα12 and Gα13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by Gα12 and Gα13. A deficiency of Gα12, but not of Gα13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, Gα12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by Gα12 gene knockout. Gα12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did Gα13 deficiency. The absence of Gα12, but not of Gα13, increased protein kinase C δ (PKC δ) activation and the PKC δ-mediated serine phosphorylation of Nrf2. Gα13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by Gα12 deficiency, suggesting that relief from Gα12 repression leads to the Gα13-mediated activation of Nrf2. Constitutive activation of Gα13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC δ activation, corroborating positive regulation by Gα13. In summary, Gα12 and Gα13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas Gα13 regulates Rho-PKC δ-mediated Nrf2 phosphorylation, which is negatively balanced by Gα12.

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