Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell Biol
1996 Jan 01;161:121-9. doi: 10.1128/MCB.16.1.121.
Show Gene links
Show Anatomy links
The AD1 transactivation domain of E2A contains a highly conserved helix which is required for its activity in both Saccharomyces cerevisiae and mammalian cells.
Massari ME
,
Jennings PA
,
Murre C
.
???displayArticle.abstract???
A conserved region, designated the AD1 domain, is present in a class of helix-loop-helix (HLH) proteins, E proteins, that includes E12, E47, HEB, E2-2, and a Xenopus laevis HLH protein closely related to E12. We demonstrate that the AD1 domain in E2A and the conserved region of E2-2 activate transcription in both yeast and mammalian cells. The AD1 domain contains a highly conserved putative helix that is crucial for its transactivation properties. Circular dichroism spectroscopy data show that AD1 is structured and contains distinctive helical properties. In addition, we show that a synthetic peptide corresponding to the conserved region is unstructured in aqueous solution at neutral pH but can adopt an alpha-helical conformation in the presence of the hydrophobic solvent trifluoroethanol. Amino acid substitutions that destabilize the helix abolish the transactivation ability of the AD1 domain. Both structural and functional analyses of AD1 reveal striking similarities to the acidic class of activators. Remarkably, when wild-type and mutant proteins are expressed in mammalian cells and Saccharomyces cerevisiae, identical patterns of transactivation are observed, suggesting that the target molecule is conserved between S. cerevisiae and mammals. These data show that transactivation by E proteins is mediated, in part, by a strikingly conserved peptide that has the ability to form a helix in a hydrophobic solvent. We propose that the unstructured domain may become helical upon interaction with its cellular target molecule.
Altschul,
Basic local alignment search tool.
1990, Pubmed
Altschul,
Basic local alignment search tool.
1990,
Pubmed
Aronheim,
The E2A gene product contains two separable and functionally distinct transcription activation domains.
1993,
Pubmed
Bain,
E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements.
1994,
Pubmed
Caudy,
daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex.
1988,
Pubmed
Caudy,
The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila.
1988,
Pubmed
Chou,
Prediction of protein conformation.
1974,
Pubmed
Cline,
The affairs of daughterless and the promiscuity of developmental regulators.
1989,
Pubmed
Cordle,
Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins.
1991,
Pubmed
Corneliussen,
Helix-loop-helix transcriptional activators bind to a sequence in glucocorticoid response elements of retrovirus enhancers.
1991,
Pubmed
Cronmiller,
Molecular characterization of daughterless, a Drosophila sex determination gene with multiple roles in development.
1988,
Pubmed
Dahlman-Wright,
Structural characterization of a minimal functional transactivation domain from the human glucocorticoid receptor.
1995,
Pubmed
Donaldson,
Purification and characterization of the carboxyl-terminal transactivation domain of Vmw65 from herpes simplex virus type 1.
1992,
Pubmed
Durfee,
The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.
1993,
Pubmed
Garnier,
Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins.
1978,
Pubmed
Gill,
Calculation of protein extinction coefficients from amino acid sequence data.
1989,
Pubmed
Henthorn,
Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif.
1990,
Pubmed
Hu,
HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.
1992,
Pubmed
Hunger,
Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia.
1992,
Pubmed
Inaba,
Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.
1992,
Pubmed
Ito,
Transformation of intact yeast cells treated with alkali cations.
1983,
Pubmed
Johnson,
Circular dichroism and its empirical application to biopolymers.
1985,
Pubmed
Johnson,
Protein secondary structure and circular dichroism: a practical guide.
1990,
Pubmed
Kamps,
A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL.
1990,
Pubmed
Lassar,
Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo.
1991,
Pubmed
Ma,
A new class of yeast transcriptional activators.
1987,
Pubmed
Mitchell,
Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins.
1989,
Pubmed
Monica,
Transformation properties of the E2a-Pbx1 chimeric oncoprotein: fusion with E2a is essential, but the Pbx1 homeodomain is dispensable.
1994,
Pubmed
Murre,
A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins.
1989,
Pubmed
Murre,
Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.
1989,
Pubmed
Murre,
Structure and function of helix-loop-helix proteins.
1994,
Pubmed
Murre,
B-cell- and myocyte-specific E2-box-binding factors contain E12/E47-like subunits.
1991,
Pubmed
Nelson,
Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs.
1990,
Pubmed
Nourse,
Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.
1990,
Pubmed
O'Hare,
Structural studies of the acidic transactivation domain of the Vmw65 protein of herpes simplex virus using 1H NMR.
1992,
Pubmed
Peverali,
Regulation of G1 progression by E2A and Id helix-loop-helix proteins.
1994,
Pubmed
Quong,
A new transcriptional-activation motif restricted to a class of helix-loop-helix proteins is functionally conserved in both yeast and mammalian cells.
1993,
Pubmed
Rashbass,
The DNA-binding protein E12 co-operates with XMyoD in the activation of muscle-specific gene expression in Xenopus embryos.
1992,
Pubmed
,
Xenbase
Sawada,
A heterodimer of HEB and an E12-related protein interacts with the CD4 enhancer and regulates its activity in T-cell lines.
1993,
Pubmed
Schlissel,
Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line.
1991,
Pubmed
Schmitz,
Structural and functional analysis of the NF-kappa B p65 C terminus. An acidic and modular transactivation domain with the potential to adopt an alpha-helical conformation.
1994,
Pubmed
Sun,
An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers.
1991,
Pubmed
Van Hoy,
The acidic activation domains of the GCN4 and GAL4 proteins are not alpha helical but form beta sheets.
1993,
Pubmed
Wang,
Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast.
1993,
Pubmed
Wülbeck,
The HLH domain of a zebrafish HE12 homologue can partially substitute for functions of the HLH domain of Drosophila DAUGHTERLESS.
1994,
Pubmed
Yaffe,
Two nuclear mutations that block mitochondrial protein import in yeast.
1984,
Pubmed
Yoshihara,
E2A-HLF-mediated cell transformation requires both the trans-activation domains of E2A and the leucine zipper dimerization domain of HLF.
1995,
Pubmed
Zhuang,
The helix-loop-helix gene E2A is required for B cell formation.
1994,
Pubmed
