Interaction of cisplatin with a CCHC zinc finger motif

2013 ◽  
Vol 19 (4) ◽  
pp. 227-232 ◽  
Author(s):  
Maria Antonietta Castiglione Morelli ◽  
Angela Ostuni ◽  
Pier Luigi Cristinziano ◽  
Diego Tesauro ◽  
Alfonso Bavoso
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Motif ◽  
Cchc Zinc Finger

scholarly journals The N-Terminal CCHC Zinc Finger Motif Mediates Homodimerization of Transcription Factor BCL11B

2017 ◽  
Vol 38 (5) ◽  
Author(s):  
Piotr Grabarczyk ◽  
Passorn Winkler ◽  
Martin Delin ◽  
Praveen K. Sappa ◽  
Sander Bekeschus ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
De Novo ◽  
Germ Line ◽  
Affinity Purification ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Dominant Negative ◽  
Zinc Finger Motif ◽  
Cchc Zinc Finger

ABSTRACT The BCL11B gene encodes a Krüppel-like, sequence-specific zinc finger (ZF) transcription factor that acts as either a repressor or an activator, depending on its posttranslational modifications. The importance of BCL11B in numerous biological processes in multiple organs has been well established in mouse knockout models. The phenotype of the first de novo monoallelic germ line missense mutation in the BCL11B gene (encoding N441K) strongly implies that the mutant protein acts in a dominant-negative manner by neutralizing the unaffected protein through the formation of a nonfunctional dimer. Using a Förster resonance energy transfer-assisted fluorescence-activated cell sorting (FACS-FRET) assay and affinity purification followed by mass spectrometry (AP-MS), we show that the N-terminal CCHC zinc finger motif is necessary and sufficient for the formation of the BCL11B dimer. Mutation of the CCHC ZF in BCL11B abolishes its transcription-regulatory activity. In addition, unlike wild-type BCL11B, this mutant is incapable of inducing cell cycle arrest and protecting against DNA damage-driven apoptosis. Our results confirm the BCL11B dimerization hypothesis and prove its importance for BCL11B function. By mapping the relevant regions to the CCHC domain, we describe a previously unidentified mechanism of transcription factor homodimerization.

scholarly journals The LIM/double zinc-finger motif functions as a protein dimerization domain.

1994 ◽  
Vol 91 (22) ◽  
pp. 10655-10659 ◽  
Author(s):  
R. Feuerstein ◽  
X. Wang ◽  
D. Song ◽  
N. E. Cooke ◽  
S. A. Liebhaber
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Motif ◽  
Dimerization Domain ◽  
Protein Dimerization

muscleblind, a gene required for photoreceptor differentiation in Drosophila, encodes novel nuclear Cys3His-type zinc-finger-containing proteins

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4321-4331 ◽  
Author(s):  
G. Begemann ◽  
N. Paricio ◽  
R. Artero ◽  
I. Kiss ◽  
M. Perez-Alonso ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Zinc Finger ◽  
Molecular Analysis ◽  
Neural Differentiation ◽  
General Factor ◽  
Lethal Gene ◽  
Zinc Finger Motif ◽  
Embryonic Lethal ◽  
Phenotype Analysis ◽  
Mutant Cells

We have isolated the embryonic lethal gene muscleblind (mbl) as a suppressor of the sev-svp2 eye phenotype. Analysis of clones mutant for mbl during eye development shows that it is autonomously required for photoreceptor differentiation. Mutant cells are recruited into developing ommatidia and initiate neural differentiation, but they fail to properly differentiate as photoreceptors. Molecular analysis reveals that the mbl locus is large and complex, giving rise to multiple different proteins with common 5′ sequences but different carboxy termini. Mbl proteins are nuclear and share a Cys3His zinc-finger motif which is also found in the TIS11/NUP475/TTP family of proteins and is highly conserved in vertebrates and invertebrates. Functional analysis of mbl, the observation that it also dominantly suppresses the sE-Jun(Asp) gain-of-function phenotype and the phenotypic similarity to mutants in the photoreceptor-specific glass gene suggest that mbl is a general factor required for photoreceptor differentiation.

Folding and immunogenicity of a loop-structured peptide using the zinc-finger motif

Peptides 1992 ◽  
1993 ◽  
pp. 561-562 ◽  
Author(s):  
Susan F. Kobs-Conrad ◽  
Ann Marie DiGeorge ◽  
Hyosil Lee ◽  
Pravin T. P. Kaumaya
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Motif

scholarly journals A single zinc finger motif in the silencing factor REST represses the neural-specific type II sodium channel promoter

1997 ◽  
Vol 94 (4) ◽  
pp. 1177-1182 ◽  
Author(s):  
J. Tapia-Ramirez ◽  
B. J. L. Eggen ◽  
M. J. Peral-Rubio ◽  
J. J. Toledo-Aral ◽  
G. Mandel
Keyword(s):  
Sodium Channel ◽  
Zinc Finger ◽  
Type Ii ◽  
Zinc Finger Motif

P1608Inhibition of GATA4 dimerization suppress hypertrophic responses

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Shimizu ◽  
Y Sunagawa ◽  
K Hara ◽  
A Hishiki ◽  
Y Katanasaka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dna Binding ◽  
Cardiac Hypertrophy ◽  
Zinc Finger ◽  
Therapeutic Target ◽  
Transcriptional Activity ◽  
Luciferase Assay ◽  
Zinc Finger Motif ◽  
Zinc Finger Domain ◽  
Acetylation Site

Abstract Introduction Hypertrophic signals eventually reach the nuclei of cardiomyocytes, change patterns of gene expression, and cause the development of heart failure. During the development of heart failure, intrinsic histone acetyltransferase called p300 induce GATA4 acetylation. Acetylated GATA4 increases its DNA binding, up-regulates cardiac hypertrophic response genes, and lead to heart failure. A zinc finger protein, GATA4 is the transcription factor that expression level is high in heart. It has been reported that GATA1, the same GATA family, regulates transcriptional activity through its homo-dimerization. However, GATA4 homo-dimerization and its relationship to hypertrophic responses are still unknown. Purpose To clarify the relationship between GATA4 homo-dimerization and transcriptional activity and investigate whether inhibition of this homo-dimerization become therapeutic target for cardiac hypertrophy. Methods GST pull-down and DNA pull-down assay were performed using GST fusion full length and deletion mutants of GATA4 and biotin-conjugated ET-1 promoter probe including a GATA element. Recombinant C-zinc finger domain (256–326), including C-zinc finger motif (256–295) and acetylation site (308–326) was cross-linked using glutaraldehyde and subjected to silver staining. An expression plasmid with three GATA4-acetylation site mutant-conjugated with nuclear localization sequence (3xG4D) was constructed. Immunoprecipitation and western blotting were performed using nuclear extract from HEK293T cells expressing p300, GATA4, and 3xG4D. Luciferase assay was using ANF and ET-1 promoter sequences. Neonatal rat cultured cardiomyocyte expressed 3xG4D and then stimulated with phenylephrine (PE) for 48 hours. Next cardiomyocytes stained with α-actinin antibody and measured the cell surface area. Results The acetylation site of GATA4 was required for the dimerization of GATA4. But, C-zinc finger motif (256–295) and the acetylation site were required for the DNA binding. Recombinant C-zinc finger domain formed not only a homo-dimer but also a multimer. Co-expression of p300 increased the formation of homo-dimer as well as the acetylation of GATA4 in HEK293T cells. The GATA4 homo-dimer was disrupted by acetyl-deficient GATA4 or HAT-deficient p300 mutant. Overexpression of 3xG4D prevented the dimerization of GATA4, but not acetylation of GATA4. The result of luciferase assay showed that overexpression of 3xG4D prevented p300/GATA-induced ANF and ET-1 promoter activities. Furthermore, overexpression of 3xG4D inhibited phenylephrine-induced cardiomyocyte hypertrophy. Conclusions These results suggest that GATA4 dimerization may play an important role in hypertrophy-response gene activation. Thus, it is likely that inhabitation of GATA4 dimerization become therapeutic target for cardiac hypertrophy.

scholarly journals Restriction of Viral Replication by Mutation of the Influenza Virus Matrix Protein

2002 ◽  
Vol 76 (24) ◽  
pp. 13055-13061 ◽  
Author(s):  
Teresa Liu ◽  
Zhiping Ye
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Viral Replication ◽  
Zinc Finger ◽  
Nuclear Export ◽  
Matrix Protein ◽  
Reverse Genetics ◽  
Rna Binding ◽  
Viral Assembly ◽  
Zinc Finger Motif

ABSTRACT The matrix protein (M1) of influenza virus plays an essential role in viral assembly and has a variety of functions, including association with influenza virus ribonucleoprotein (RNP). Our previous studies show that the association of M1 with viral RNA and nucleoprotein not only promotes formation of helical RNP but also is required for export of RNP from the nucleus during viral replication. The RNA-binding domains of M1 have been mapped to two independent regions: a zinc finger motif at amino acid positions 148 to 162 and a series of basic amino acids (RKLKR) at amino acid positions 101 to 105, which is also involved in RNP-binding activity. To further understand the role of the RNP-binding domain of M1 in viral assembly and replication, mutations in the coding sequences of RKLKR and the zinc finger motif of M1 were constructed using a PCR technique and introduced into wild-type influenza virus by reverse genetics. Altering the zinc finger motif of M1 only slightly affected viral growth. Substitution of Arg with Ser at position 101 or 105 of RKLKR did not have a major impact on nuclear export of RNP or viral replication. In contrast, deletion of RKLKR or substitution of Lys with Asn at position 102 or 104 of RKLKR resulted in a lethal mutation. These results indicate that the RKLKR domain of M1 protein plays an important role in viral replication.

A Poxvirus Protein with a RING Zinc Finger Motif Is of Crucial Importance for Virulence

Virology ◽  
1994 ◽  
Vol 198 (1) ◽  
pp. 118-128 ◽  
Author(s):  
Tania G. Senkevich ◽  
Eugene V. Koonin ◽  
R.Mark L. Buller
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Motif ◽  
Crucial Importance ◽  
Ring Zinc Finger
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