Cap ‘n’ collar B cooperates with a small Maf subunit to specify pharyngeal development and suppress deformed homeotic function in the Drosophila head

Development ◽  
2000 ◽  
Vol 127 (18) ◽  
pp. 4023-4037 ◽  
Author(s):  
A. Veraksa ◽  
N. McGinnis ◽  
X. Li ◽  
J. Mohler ◽  
W. McGinnis
Keyword(s):  
Transcriptional Activation ◽  
Protein Function ◽  
Leucine Zipper ◽  
Suppressive Effect ◽  
Basic Leucine Zipper ◽  
Transcriptional Activation Domain ◽  
Amino Terminal ◽  
Culture Cells ◽  
Mandibular Segment ◽  
Direct Binding

The basic-leucine zipper protein Cap ‘n’ collar B (CncB) suppresses the segmental identity function of the Hox gene Deformed (Dfd) in the mandibular segment of Drosophila embryos. CncB is also required for proper development of intercalary, labral and mandibular structures. In this study, we provide evidence that the CncB-mediated suppression of Dfd requires the Drosophila homolog of the mammalian small Maf proteins, Maf-S, and that the suppression occurs even in the presence of high amounts of Dfd protein. Interestingly, the CncB/Maf-S suppressive effect can be partially reversed by overexpression of Homothorax (Hth), suggesting that Hth and Extradenticle proteins antagonize the effects of CncB/Maf-S on Dfd function in the mandibular segment. In embryos, multimers of simple CncB/Maf-S heterodimer sites are transcriptionally activated in response to CncB, and in tissue culture cells the amino-terminal domain of CncB acts as a strong transcriptional activation domain. There are no good matches to CncB/Maf binding consensus sites in the known elements that are activated in response to Dfd and repressed in a CncB-dependent fashion. This suggests that some of the suppressive effect of CncB/Maf-S proteins on Dfd protein function might be exerted indirectly, while some may be exerted by direct binding to as yet uncharacterized Dfd response elements. We also show that ectopic CncB is sufficient to transform ventral epidermis in the trunk into repetitive arrays of ventral pharynx. We compare the functions of CncB to those of its vertebrate and invertebrate homologs, p45 NF-E2, Nrf and Skn-1 proteins, and suggest that the pharynx selector function of CncB is highly conserved on some branches of the evolutionary tree.

scholarly journals Regulation of the Amino-Terminal Transcription Activation Domain of Progesterone Receptor by a Cofactor-Induced Protein Folding Mechanism

2005 ◽  
Vol 25 (20) ◽  
pp. 8792-8808 ◽  
Author(s):  
Suzanne E. Wardell ◽  
Stanley C. Kwok ◽  
Lori Sherman ◽  
Robert S. Hodges ◽  
Dean P. Edwards
Keyword(s):  
Progesterone Receptor ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Leucine Zipper ◽  
Activation Domain ◽  
Basic Leucine Zipper ◽  
Transcriptional Activation Domain ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Helical Content

ABSTRACT We previously identified a small basic leucine zipper (bZIP) protein, Jun dimerization protein 2 (JDP-2), that acts as a coregulator of the N-terminal transcriptional activation domain of progesterone receptor (PR). We show here that JDP-2, through interaction with the DNA binding domain (DBD), induces or stabilizes structure in the N-terminal domain in a manner that correlates with JDP-2 stimulation of transcriptional activity. Circular dichroism spectroscopy experiments showed that JDP-2 interaction caused a significant increase in overall helical content of a two-domain PR polypeptide containing the N-terminal domain and DBD and that the change in structure resides primarily in the N-terminal domain. Thermal melt curves showed that the JDP-2/PR complex is significantly more stable than either protein alone, and partial proteolysis confirmed that JDP-2 interaction alters conformation of the N-terminal domain of PR. Functional analysis of N-terminal domain mutants and receptor chimeras provides evidence that the stimulatory effect of JDP-2 on transcriptional activity of PR is mediated through an interdomain communication between the DBD and the N-terminal domain and that transcriptional activity and functional response to JDP-2 are mediated by multiple elements of the N-terminal domain as opposed to a discrete region.

scholarly journals The proto-oncogene HLF and the related basic leucine zipper protein TEF display highly similar DNA-binding and transcriptional regulatory properties

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4607-4617 ◽  
Author(s):  
SP Hunger ◽  
S Li ◽  
MZ Fall ◽  
L Naumovski ◽  
ML Cleary
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Lymphoblastic Leukemia ◽  
Consensus Sequence ◽  
Basic Leucine Zipper ◽  
Amino Terminal ◽  
Transcriptional Regulatory ◽  
Regulatory Properties

Genes encoding transcription factors are frequently altered by chromosomal translocations in acute lymphoblastic leukemia (ALL), suggesting that aberrant transcriptional regulation plays a prominent role in leukemogenesis. E2A-hepatic leukemia factor (HLF), a chimeric transcription factor created by the t(17;19), consists of the amino terminal portion of E2A proteins, including two experimentally defined transcriptional activation domains (TADs), fused to the HLF DNA binding and protein dimerization basic leucine zipper (bZIP) domain. To understand the mechanisms by which E2A-HLF induces leukemia and the crucial functions contributed by each constituent of the chimera, it is essential to define the normal transcriptional regulatory properties of HLF and related bZIP proteins. To address these questions, we cloned the human homologue of TEF/VBP, a bZIP protein closely related to HLF. Using a binding site selection assay, we found that TEF bound preferentially to the consensus sequence 5′-GTTACGTAAT-3′, which is identical to the previously determined HLF recognition site. TEF and HLF activated transcription of consensus site-containing reporter genes in several different cell types with similar potencies. Using GAL4 chimeric proteins, a TAD was mapped to a discrete approximate 40 amino acid region of TEF and HLF within which they share 72% amino acid identity and 85% similarity. The TEF/HLF activation domain (THAD) has a predicted helical secondary structure, but shares no sequence homology with previously reported TADs. The THAD contained most, if not all, of the transcriptional activation properties present in both TEF and HLF and its deletion completely abrogated transcriptional activity of TEF and HLF in both mammalian cells and yeast. Thus, TEF and HLF share indistinguishable DNA-binding and transcriptional regulatory properties, whose alteration in leukemia may be pathogenetically important.

scholarly journals Functional and Placental Expression Analysis of the Human NRF3 Transcription Factor

2005 ◽  
Vol 19 (1) ◽  
pp. 125-137 ◽  
Author(s):  
Benoı̂t Chénais ◽  
Anna Derjuga ◽  
Wael Massrieh ◽  
Kristy Red-Horse ◽  
Valerie Bellingard ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Related Factor ◽  
Nuclear Factor ◽  
Basic Leucine Zipper ◽  
Transcriptional Activation Domain ◽  
Functional Studies ◽  
Recognition Element ◽  
Protein Levels

Abstract Members of the Maf protooncogene and cap’n’ collar families of basic-leucine zipper transcription factors play important roles in development, differentiation, oncogenesis, and stress signaling. In this study, we performed an in vivo protein-protein interaction screen to search for novel partners of the small Maf proteins. Using full-length human MAFG protein as bait, we identified the human basic-leucine zipper protein NRF3 [NF-E2 (nuclear factor erythroid 2)-related factor 3] as an interaction partner. Transfection studies confirmed that NRF3 is able to dimerize with MAFG. The resulting NRF3/MAFG heterodimer recognizes nuclear factor-erythroid 2/Maf recognition element-type DNA-binding motifs. Functional analysis revealed the presence of a strong transcriptional activation domain in the center region of the NRF3 protein. We found that NRF3 transcripts are present in placental chorionic villi from at least week 12 of gestation on through term. In particular, NRF3 is highly expressed in primary placental cytotrophoblasts, but not in placental fibroblasts. The human choriocarcinoma cell lines BeWo and JAR, derived from trophoblastic tumors of the placenta, also strongly express NRF3 transcripts. We generated a NRF3-specific antiserum and identified NRF3 protein in placental choriocarcinoma cells. Furthermore, we showed that NRF3 transcript and protein levels are induced by TNF-α in JAR cells. Our functional studies suggest that human NRF3 is a potent transcriptional activator. Finally, our expression and induction analyses hint at a possible role of Nrf3 in placental gene expression and development.

scholarly journals Interaction of ATF6 and serum response factor.

1997 ◽  
Vol 17 (9) ◽  
pp. 4957-4966 ◽  
Author(s):  
C Zhu ◽  
F E Johansen ◽  
R Prywes
Keyword(s):  
Reporter Gene ◽  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Serum Response Factor ◽  
Response Factor ◽  
Basic Leucine Zipper ◽  
Transcriptional Activation Domain ◽  
Activation Of Transcription ◽  
Serum Response

Serum response factor (SRF) is a transcription factor which binds to the serum response element (SRE) in the c-fos promoter. It is required for regulated expression of the c-fos gene as well as other immediate-early genes and some tissue-specific genes. To better understand the regulation of SRF, we used a yeast interaction assay to screen a human HeLa cell cDNA library for SRF-interacting proteins. ATF6, a basic-leucine zipper protein, was isolated by binding to SRF and in particular to its transcriptional activation domain. The binding of ATF6 to SRF was also detected in vitro. An ATF6-VP16 chimera activated expression of an SRE reporter gene in HeLa cells, suggesting that ATF6 can interact with endogenous SRF. More strikingly, an antisense ATF6 construct reduced serum induction of a c-fos reporter gene, suggesting that ATF6 is involved in activation of transcription by SRF. ATF6 was previously partially cloned as a member of the ATF family. The complete cDNA of ATF6 was isolated, and its expression pattern was described.

scholarly journals Proteasome activator PA28γ stimulates degradation of GSK3-phosphorylated insulin transcription activator MAFA

2011 ◽  
Vol 47 (1) ◽  
pp. 119-127 ◽  
Author(s):  
Kenichi Kanai ◽  
Shinsaku Aramata ◽  
Sayo Katakami ◽  
Kunio Yasuda ◽  
Kohsuke Kataoka
Keyword(s):  
Transcriptional Activation ◽  
Map Kinases ◽  
Leucine Zipper ◽  
Cell Function ◽  
Transcription Activator ◽  
Basic Leucine Zipper ◽  
Amino Terminal ◽  
Insulin Promoter ◽  
Β Cell Function ◽  
Amino Terminal Domain

MAFA is a member of the MAF family of basic leucine zipper transcription factors and is a critical regulator of insulin gene expression and islet β-cell function. To be degraded by the proteasome, MAFA must be phosphorylated by GSK3 and MAP kinases at multiple serine and threonine residues (Ser49, Thr53, Thr57, Ser61, and Ser65) within its amino-terminal domain. In this study, we report that MAFA degradation is stimulated by PA28γ (REGγ and PSME3), a member of a family of proteasome activators that bind and activate the 20S proteasome. To date, only a few PA28γ-proteasome pathway substrates have been identified, including steroid receptor coactivator 3 (SRC3) and the cell cycle inhibitor p21 (CIP1). PA28γ binds to MAFA, induces its proteasomal degradation, and thereby attenuates MAFA-driven transcriptional activation of the insulin promoter. Co-expression of GSK3 enhanced the PA28γ-mediated degradation of MAFA, but mutants that contained alanine substitutions at the MAFA phosphorylation sites did not bind PA28γ and were resistant to degradation. We also found that a PA28γ mutant (N151Y) that did not stimulate p21 degradation enhanced MAFA degradation, and another mutant (K188D) that promoted greater p21 degradation did not enhance MAFA degradation. These results suggest that PA28γ stimulates MAFA degradation through a novel molecular mechanism that is distinct from that for the degradation of p21.

scholarly journals Sir Proteins, Rif Proteins, and Cdc13p BindSaccharomyces Telomeres In Vivo

1998 ◽  
Vol 18 (9) ◽  
pp. 5600-5608 ◽  
Author(s):  
Brenda D. Bourns ◽  
Mary Kate Alexander ◽  
Andrew M. Smith ◽  
Virginia A. Zakian
Keyword(s):  
Reporter Gene ◽  
Transcriptional Activation ◽  
Binding Proteins ◽  
Position Effect ◽  
Initiation Site ◽  
Telomeric Sequence ◽  
Transcriptional Activation Domain ◽  
Amino Terminal ◽  
Sir Proteins

ABSTRACT Although a surprisingly large number of genes affect yeast telomeres, in most cases it is not known if their products act directly or indirectly. We describe a one-hybrid assay for telomere binding proteins and use it to establish that six proteins that affect telomere structure or function but which had not been shown previously to bind telomeres in vivo are indeed telomere binding proteins. A promoter-defective allele of HIS3 was placed adjacent to a chromosomal telomere. Candidate proteins fused to a transcriptional activation domain were tested for the ability to activate transcription of the telomere-linked HIS3 gene. Using this system, Rif1p, Rif2p, Sir2p, Sir3p, Sir4p, and Cdc13p were found to be in vivo telomere binding proteins. None of the proteins activated the same reporter gene when it was at an internal site on the chromosome. Moreover, Cdc13p did not activate the reporter gene when it was adjacent to an internal tract of telomeric sequence, indicating that Cdc13p binding was telomere limited in vivo. The amino-terminal 20% of Cdc13p was sufficient to target Cdc13p to a telomere, suggesting that its DNA binding domain was within this portion of the protein. Rap1p, Rif1p, Rif2p, Sir4p, and Cdc13p activated the telomeric reporter gene in a strain lacking Sir3p, which is essential for telomere position effect (TPE). Thus, the telomeric association of these proteins did not require any of the chromatin features necessary for TPE. The data support models in which the telomere acts as an initiation site for TPE by recruiting silencing proteins to the chromosome end.

scholarly journals Characteristics and Expression Pattern of MYC Genes in Triticum aestivum, Oryza sativa, and Brachypodium distachyon

Plants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 274 ◽  
Author(s):  
Shoukun Chen ◽  
Hongyan Zhao ◽  
Tengli Luo ◽  
Yue Liu ◽  
Xiaojun Nie ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Brachypodium Distachyon ◽  
Expression Patterns ◽  
Terminal Region ◽  
Gene Promoters ◽  
Interaction Domain ◽  
Specific Expression ◽  
Systematic Analysis ◽  
Transcriptional Activation Domain

Myelocytomatosis oncogenes (MYC) transcription factors (TFs) belong to basic helix-loop-helix (bHLH) TF family and have a special bHLH_MYC_N domain in the N-terminal region. Presently, there is no detailed and systematic analysis of MYC TFs in wheat, rice, and Brachypodium distachyon. In this study, 26 TaMYC, 7 OsMYC, and 7 BdMYC TFs were identified and their features were characterized. Firstly, they contain a JAZ interaction domain (JID) and a putative transcriptional activation domain (TAD) in the bHLH_MYC_N region and a BhlH region in the C-terminal region. In some cases, the bHLH region is followed by a leucine zipper region; secondly, they display tissue-specific expression patterns: wheat MYC genes are mainly expressed in leaves, rice MYC genes are highly expressed in stems, and B. distachyon MYC genes are mainly expressed in inflorescences. In addition, three types of cis-elements, including plant development/growth-related, hormone-related, and abiotic stresses-related were identified in different MYC gene promoters. In combination with the previous studies, these results indicate that MYC TFs mainly function in growth and development, as well as in response to stresses. This study laid a foundation for the further functional elucidation of MYC genes.

scholarly journals The Varicella-Zoster Virus (VZV) ORF9 Protein Interacts with the IE62 Major VZV Transactivator

2006 ◽  
Vol 81 (2) ◽  
pp. 761-774 ◽  
Author(s):  
Cristian Cilloniz ◽  
Wallen Jackson ◽  
Charles Grose ◽  
Donna Czechowski ◽  
John Hay ◽  
...  
Keyword(s):  
Amino Acids ◽  
Confocal Microscopy ◽  
Varicella Zoster Virus ◽  
Transcriptional Activation ◽  
Protein Function ◽  
Transfected Cells ◽  
Varicella Zoster ◽  
Transcriptional Activation Domain ◽  
Infected Cells ◽  
Orf9 Protein

ABSTRACT The varicella-zoster virus (VZV) ORF9 protein is a member of the herpesvirus UL49 gene family but shares limited identity and similarity with the UL49 prototype, herpes simplex virus type 1 VP22. ORF9 mRNA is the most abundantly expressed message during VZV infection; however, little is known concerning the functions of the ORF9 protein. We have found that the VZV major transactivator IE62 and the ORF9 protein can be coprecipitated from infected cells. Yeast two-hybrid analysis localized the region of the ORF9 protein required for interaction with IE62 to the middle third of the protein encompassing amino acids 117 to 186. Protein pull-down assays with GST-IE62 fusion proteins containing N-terminal IE62 sequences showed that amino acids 1 to 43 of the acidic transcriptional activation domain of IE62 can bind recombinant ORF9 protein. Confocal microscopy of transiently transfected cells showed that in the absence of other viral proteins, the ORF9 protein was localized in the cytoplasm while IE62 was localized in the nucleus. In VZV-infected cells, the ORF9 protein was localized to the cytoplasm whereas IE62 exhibited both nuclear and cytoplasmic localization. Cotransfection of plasmids expressing ORF9, IE62, and the viral ORF66 kinase resulted in significant colocalization of ORF9 and IE62 in the cytoplasm. Coimmunoprecipitation experiments with antitubulin antibodies indicate the presence of ORF9-IE62-tubulin complexes in infected cells. Colocalization of ORF9 and tubulin in transfected cells was visualized by confocal microscopy. These data suggest a model for ORF9 protein function involving complex formation with IE62 and possibly other tegument proteins in the cytoplasm at late times in infection.

scholarly journals A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation

2007 ◽  
Vol 402 (1) ◽  
pp. 163-173 ◽  
Author(s):  
Alex B. Lopez ◽  
Chuanping Wang ◽  
Charlie C. Huang ◽  
Ibrahim Yaman ◽  
Yi Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
Amino Acid Starvation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Basic Leucine Zipper

The adaptive response to amino acid limitation in mammalian cells inhibits global protein synthesis and promotes the expression of proteins that protect cells from stress. The arginine/lysine transporter, cat-1, is induced during amino acid starvation by transcriptional and post-transcriptional mechanisms. It is shown in the present study that the transient induction of cat-1 transcription is regulated by the stress response pathway that involves phosphorylation of the translation initiation factor, eIF2 (eukaryotic initiation factor-2). This phosphorylation induces expression of the bZIP (basic leucine zipper protein) transcription factors C/EBP (CCAAT/enhancer-binding protein)-β and ATF (activating transcription factor) 4, which in turn induces ATF3. Transfection experiments in control and mutant cells, and chromatin immunoprecipitations showed that ATF4 activates, whereas ATF3 represses cat-1 transcription, via an AARE (amino acid response element), TGATGAAAC, in the first exon of the cat-1 gene, which functions both in the endogenous and in a heterologous promoter. ATF4 and C/EBPβ activated transcription when expressed in transfected cells and they bound as heterodimers to the AARE in vitro. The induction of transcription by ATF4 was inhibited by ATF3, which also bound to the AARE as a heterodimer with C/EBPβ. These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism.

Interactions among LRF-1, JunB, c-Jun, and c-Fos define a regulatory program in the G1 phase of liver regeneration

1992 ◽  
Vol 12 (10) ◽  
pp. 4654-4665
Author(s):  
J C Hsu ◽  
R Bravo ◽  
R Taub
Keyword(s):  
Cyclic Amp ◽  
Transcriptional Activation ◽  
Leucine Zipper ◽  
G1 Phase ◽  
Basic Leucine Zipper ◽  
Relative Level ◽  
Response Element ◽  
Complex Interactions ◽  
Cyclic Amp Response Element ◽  
The Many

In regenerating liver, a physiologically normal model of cell growth, LRF-1, JunB, c-Jun, and c-Fos among Jun/Fos/LRF-1 family members are induced posthepatectomy. In liver cells, high levels of c-Fos/c-Jun, c-Fos/JunB, LRF-1/c-Jun, and LRF-1/JunB complexes are present for several hours after the G0/G1 transition, and the relative level of LRF-1/JunB complexes increases during G1. We provide evidence for dramatic differences in promoter-specific activation by LRF-1- and c-Fos-containing complexes. LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. LRF-1/c-Jun, c-Fos/c-Jun, and c-Fos/JunB activate specific AP-1 and ATF site-containing promoters, and in contrast, LRF-1/JunB potently represses c-Fos- and c-Jun-mediated activation of these promoters. Repression is dependent on a region in LRF-1 that includes amino acids 40 to 84 (domain R) and the basic/leucine zipper domain. As the relative level of LRF-1/JunB complexes increases posthepatectomy, c-Fos/Jun-mediated ATF and AP-1 site activation is likely to decrease with simultaneous transcriptional activation of the many liver-specific genes whose promoters contain cyclic AMP response element sites. Thus, through complex interactions among LRF-1, JunB, c-Jun, and c-Fos, control of delayed gene expression may be established for extended times during the G1 phase of hepatic growth.

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