scholarly journals Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F.

1992 ◽  
Vol 12 (12) ◽  
pp. 5620-5631 ◽  
Author(s):  
B Shan ◽  
X Zhu ◽  
P L Chen ◽  
T Durfee ◽  
Y Yang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
T Antigen ◽  
Transactivation Domain ◽  
Recognition Sequence ◽  
Cellular Genes ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Transcription Factor E2f

The retinoblastoma protein interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function. To identify these proteins, we isolated nine distinct clones by direct screening of cDNA expression libraries using purified RB protein as a probe. One of these clones, Ap12, is expressed predominantly at the G1-S boundary and in the S phase of the cell cycle. The nucleotide sequence of Ap12 has features characteristic of transcription factors. The C-terminal region binds to unphosphorylated RB in regions similar to those to which T antigen binds and contains a transactivation domain. A region containing a potential leucine zipper flanked by basic residues is able to bind an E2F recognition sequence specifically. Expression of Ap12 in mammalian cells significantly enhances E2F-dependent transcriptional activity. These results suggest that Ap12 encodes a protein with properties known to be characteristic of transcription factor E2F.

Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F

1992 ◽  
Vol 12 (12) ◽  
pp. 5620-5631
Author(s):  
B Shan ◽  
X Zhu ◽  
P L Chen ◽  
T Durfee ◽  
Y Yang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
T Antigen ◽  
Transactivation Domain ◽  
Recognition Sequence ◽  
Cellular Genes ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Transcription Factor E2f

The retinoblastoma protein interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function. To identify these proteins, we isolated nine distinct clones by direct screening of cDNA expression libraries using purified RB protein as a probe. One of these clones, Ap12, is expressed predominantly at the G1-S boundary and in the S phase of the cell cycle. The nucleotide sequence of Ap12 has features characteristic of transcription factors. The C-terminal region binds to unphosphorylated RB in regions similar to those to which T antigen binds and contains a transactivation domain. A region containing a potential leucine zipper flanked by basic residues is able to bind an E2F recognition sequence specifically. Expression of Ap12 in mammalian cells significantly enhances E2F-dependent transcriptional activity. These results suggest that Ap12 encodes a protein with properties known to be characteristic of transcription factor E2F.

The Transcription Factor E2F-1 in SV40 T Antigen-Induced Cerebellar Purkinje Cell Degeneration

1998 ◽  
Vol 12 (1-2) ◽  
pp. 16-28 ◽  
Author(s):  
Maria C. Athanasiou ◽  
Wael Yunis ◽  
Natalie Coleman ◽  
Robert Ehlenfeldt ◽  
H.Brent Clark ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Purkinje Cell ◽  
T Antigen ◽  
Cerebellar Purkinje Cell ◽  
Sv40 T Antigen ◽  
Cell Degeneration ◽  
Purkinje Cell Degeneration ◽  
Transcription Factor E2f

scholarly journals Induction of metallothionein I by phenolic antioxidants requires metal-activated transcription factor 1 (MTF-1) and zinc

2004 ◽  
Vol 380 (3) ◽  
pp. 695-703 ◽  
Author(s):  
Yongyi BI ◽  
Richard D. PALMITER ◽  
Kristi M. WOOD ◽  
Qiang MA
Keyword(s):  
Transcription Factor ◽  
Phase Ii ◽  
Leucine Zipper ◽  
Gene Promoter ◽  
Phenolic Antioxidants ◽  
Related Factor ◽  
Basic Leucine Zipper ◽  
Free Zinc ◽  
Genes Encoding ◽  
Transcription Factor 1

Phenolic antioxidants, such as tBHQ [2,5-di-(t-butyl)-1,4-hydroquinone], induce Mt1 (metallothionein 1) gene expression and accumulation of MT protein. Induction of Mt1 mRNA does not depend on protein synthesis, and correlates with oxidation–reduction functions of the antioxidants. In the present study, we analysed the biochemical pathway of the induction. Induction depends on the presence of MTF-1 (metal-activated transcription factor 1), a transcription factor that is required for metal-induced transcription of Mt1, but does not require nuclear factor erythroid 2-related factor 2, a tBHQ-activated CNC bZip (cap ‘n’ collar basic leucine zipper) protein, that is responsible for regulating genes encoding phase II drug-metabolizing enzymes. Moreover, tBHQ induces the expression of MRE-βGeo, a reporter gene driven by five metal response elements that constitute an optimal MTF-1 binding site. Reconstitution of Mtf1-null cells with MTF-1 restores induction by both zinc and tBHQ. Unlike activation of phase II genes by tBHQ, induction of Mt1 expression does not occur in the presence of EDTA, when cells are cultured in zinc-depleted medium, or in cells with reduced intracellular ‘free’ zinc due to overexpression of ZnT1, a zinc-efflux transporter, indicating that induction requires zinc. In addition, fluorescence imaging reveals that tBHQ increases cytoplasmic free zinc concentration by mobilizing intracellular zinc pools. These findings establish that phenolic antioxidants activate Mt1 transcription by a zinc-dependent mechanism, which involves MTF-1 binding to metal regulator elements in the Mt1 gene promoter.

Inhibitory Effect of the Transcription Factor Encoded by themi Mutant Allele in Cultured Mast Cells of Mice

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1189-1196 ◽  
Author(s):  
Akihiko Ito ◽  
Eiichi Morii ◽  
Dae-Ki Kim ◽  
Tatsuki R. Kataoka ◽  
Tomoko Jippo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cells ◽  
Leucine Zipper ◽  
Tryptophan Hydroxylase ◽  
Cdna Probe ◽  
Inhibitory Effect ◽  
Northern Analysis ◽  
Helix Loop Helix ◽  
Genes Encoding ◽  
Mouse Mast Cell

The mi locus of mice encodes a transcription factor of the basic-helix-loop-helix-leucine zipper protein family (MITF). The MITF encoded by the mutant mi allele (mi-MITF) deletes 1 of 4 consecutive arginines in the basic domain. The mice of mi/migenotype express mi-MITF, whereas the mice of tg/tggenotype have a transgene at the 5′ flanking region of themi gene and do not express any MITF. To investigate the function of mi-MITF in cultured mast cells (CMCs), we took two approaches. First, mRNA obtained from mi/mi CMCs ortg/tg CMCs was subtracted from complementary (c) DNA library of normal (+/+) CMCs, and the (+/+-mi/mi) and (+/+-tg/tg) subtraction libraries were obtained. When the number of clones that hybridized more efficiently with +/+ CMC cDNA probe than with mi/mi or tg/tg CMC cDNA probe was compared using Southern analysis, the number was larger in the (+/+-mi/mi) library than in the (+/+-tg/tg) library. Second, we compared mRNA expression of six genes betweenmi/mi and tg/tg CMCs by Northern analysis. The transcription of three genes encoding mouse mast cell proteases was impaired in both mi/mi and tg/tg CMCs. On the other hand, the transcription of three genes encoding c-kit receptor, tryptophan hydroxylase, and granzyme B was markedly reduced inmi/mi CMCs, but the reduction was significantly smaller intg/tg CMCs. These results indicated the inhibitory effect ofmi-MITF on the transactivation of particular genes in CMCs.

Identification and function of phosphorylation in the glucose-regulated transcription factor ChREBP

2008 ◽  
Vol 411 (2) ◽  
pp. 261-270 ◽  
Author(s):  
Nikolas G. Tsatsos ◽  
Michael N. Davies ◽  
Brennon L. O'callaghan ◽  
Howard C. Towle
Keyword(s):  
Transcription Factor ◽  
High Glucose ◽  
Leucine Zipper ◽  
De Novo ◽  
Regulatory Region ◽  
De Novo Lipogenesis ◽  
Nuclear Accumulation ◽  
Helix Loop Helix ◽  
Genes Encoding ◽  
And Function

In the liver, induction of genes encoding enzymes involved in de novo lipogenesis occurs in response to increased glucose metabolism. ChREBP (carbohydrate-response-element-binding protein) is a basic helix–loop–helix/leucine zipper transcription factor that regulates expression of these genes. To evaluate the potential role of ChREBP phosphorylation in its regulation, we used MS to identify modified residues. In the present paper, we report the detection of multiple phosphorylation sites of ChREBP expressed in hepatocytes, several of which are only observed under high-glucose conditions. Mutation of each of these serine/threonine residues of ChREBP did not alter its ability to respond to glucose. However, mutation of five N-terminal phosphoacceptor sites resulted in a major decrease in activity under high-glucose conditions. These phosphorylated residues are located within a region of ChREBP (amino acids 1–197) that is critical for glucose regulation. Mutation of Ser56 within this region to an aspartate residue resulted in increased nuclear accumulation and activity under high-glucose conditions. Together, these data suggest that ChREBP activity is regulated by complex multisite phosphorylation patterns involving its N-terminal regulatory region.

scholarly journals The Minimal Transactivation Domain of the Basic Motif-Leucine Zipper Transcription Factor NRL Interacts with TATA-binding Protein

2004 ◽  
Vol 279 (45) ◽  
pp. 47233-47241 ◽  
Author(s):  
James S. Friedman ◽  
Hemant Khanna ◽  
Prabodh K. Swain ◽  
Raphael DeNicola ◽  
Hong Cheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leucine Zipper ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Transactivation Domain

scholarly journals A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2

2005 ◽  
Vol 393 (2) ◽  
pp. 489-501 ◽  
Author(s):  
Jialiang Wang ◽  
Xiaping He ◽  
Ying Luo ◽  
Wendell G. Yarbrough
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Translational Regulation ◽  
Leucine Zipper ◽  
Binding Protein ◽  
Reading Frame ◽  
Cycle Arrest ◽  
Ubiquitin Ligase Activity ◽  
Associated Proteins ◽  
Dependent Cell

The tumour suppressor ARF (alternative reading frame) is encoded by the INK4a (inhibitor of cyclin-dependent kinase 4)/ARF locus, which is frequently altered in human tumours. ARF binds MDM2 (murine double minute 2) and releases p53 from inhibition by MDM2, resulting in stabilization, accumulation and activation of p53. Recently, ARF has been found to associate with other proteins, but, to date, little is known about ARF-associated proteins that are implicated in post-translational regulation of ARF activity. Using a yeast two-hybrid screen, we have identified a novel protein, LZAP (LXXLL/leucine-zipper-containing ARF-binding protein), that interacts with endogenous ARF in mammalian cells. In the present study, we show that LZAP reversed the ability of ARF to inhibit HDM2's ubiquitin ligase activity towards p53, but simultaneously co-operated with ARF, maintaining p53 stability and increasing p53 transcriptional activity. Expression of LZAP, in addition to ARF, increased the percentage of cells in the G1 phase of the cell cycle. Expression of LZAP also caused activation of p53 and a p53-dependent G1 cell-cycle arrest in the absence of ARF. Taken together, our data suggest that LZAP can regulate ARF biochemical and biological activity. Additionally, LZAP has p53-dependent cell-cycle effects that are independent of ARF.

scholarly journals Molecular mechanism of attenuation of heat shock transcription factor 1 activity

2019 ◽  
Author(s):  
Szymon W. Kmiecik ◽  
Laura Le Breton ◽  
Matthias P. Mayer
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Leucine Zipper ◽  
Transcriptional Response ◽  
Heat Shock Transcription Factor ◽  
Transactivation Domain ◽  
Proteotoxic Stress ◽  
Transcription Factor 1 ◽  
Over 40 Years

AbstractThe heat shock response is a universal transcriptional response to proteotoxic stress orchestrated by heat shock transcription factor Hsf1 in all eukaryotic cells. Despite over 40 years of intense research, the mechanism of HSF1 activity regulation remains poorly understood at a molecular level. In metazoa Hsf1 trimerizes upon heat shock through a leucin-zipper domain and binds to DNA. How Hsf1 is dislodged from DNA and monomerized remained enigmatic. Here, we demonstrate that trimeric Hsf1 is dissociated from DNA in vitro by Hsc70 and DnaJB1. Hsc70 acts at two distinct sites on Hsf1. Hsf1 trimers are monomerized by successive cycles of entropic pulling, unzipping the triple leucine-zipper. This process directly monitors the concentration of Hsc70 and DnaJB1. During heat shock adaptation Hsc70 first binds to the transactivation domain leading to partial attenuation of the response and subsequently, at higher concentrations, Hsc70 removes Hsf1 from DNA to restore the resting state.

Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19)

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 962-970 ◽  
Author(s):  
Kinuko Hirose ◽  
Takeshi Inukai ◽  
Jiro Kikuchi ◽  
Yusuke Furukawa ◽  
Tomokatsu Ikawa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Line ◽  
Leucine Zipper ◽  
Apoptotic Cell ◽  
Lymphoblastic Leukemia ◽  
Therapeutic Modality ◽  
Transactivation Domain ◽  
Specific Expression ◽  
Human T Cell ◽  
Primary Sample

Abstract LMO2, a critical transcription regulator of hematopoiesis, is involved in human T-cell leukemia. The binding site of proline and acidic amino acid–rich protein (PAR) transcription factors in the promoter of the LMO2 gene plays a central role in hematopoietic-specific expression. E2A-HLF fusion derived from t(17;19) in B-precursor acute lymphoblastic leukemia (ALL) has the transactivation domain of E2A and the basic region/leucine zipper domain of HLF, which is a PAR transcription factor, raising the possibility that E2A-HLF aberrantly induces LMO2 expression. We here demonstrate that cell lines and a primary sample of t(17;19)-ALL expressed LMO2 at significantly higher levels than other B-precursor ALLs did. Transfection of E2A-HLF into a non-t(17;19) B-precursor ALL cell line induced LMO2 gene expression that was dependent on the DNA-binding and transactivation activities of E2A-HLF. The PAR site in the LMO2 gene promoter was critical for E2A-HLF-induced LMO2 expression. Gene silencing of LMO2 in a t(17;19)-ALL cell line by short hairpin RNA induced apoptotic cell death. These observations indicated that E2A-HLF promotes cell survival of t(17;19)-ALL cells by aberrantly up-regulating LMO2 expression. LMO2 could be a target for a new therapeutic modality for extremely chemo-resistant t(17;19)-ALL.

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