Abstract:
:The serum response factor (SRF) and myocyte enhancer factor 2A (MEF2A) represent two human members of the MADS-box transcription factor family. Each protein has a distinct biological function which is reflected by the distinct specificities of the proteins for coregulatory protein partners and DNA-binding sites. In this study, we have investigated the mechanism of DNA binding utilized by these two related transcription factors. Although SRF and MEF2A belong to the same family and contain related DNA-binding domains, their DNA-binding mechanisms differ in several key aspects. In contrast to the dramatic DNA bending induced by SRF, MEF2A induces minimal DNA distortion. A combination of loss- and gain-of-function mutagenesis identified a single amino acid residue located at the N terminus of the recognition helices as the critical mediator of this differential DNA bending. This residue is also involved in determining DNA-binding specificity, thus indicating a link between DNA bending and DNA-binding specificity determination. Furthermore, different basic residues within the putative recognition alpha-helices are critical for DNA binding, and the role of the C-terminal extensions to the MADS box in dimerization between SRF and MEF2A also differs. These important differences in the molecular interactions of SRF and MEF2A are likely to contribute to their differing roles in the regulation of specific gene transcription.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
West AG,Shore P,Sharrocks ADdoi
10.1128/mcb.17.5.2876subject
Has Abstractpub_date
1997-05-01 00:00:00pages
2876-87issue
5eissn
0270-7306issn
1098-5549journal_volume
17pub_type
杂志文章abstract::We have identified a gene that encodes the polypeptide cytochrome b in the avian malarial parasite Plasmodium gallinaceum. The gene containing the open reading frame was found to be located on a 6.2-kilobase multimeric extrachromosomal element. The amino acid translation from this gene demonstrated significant similar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.9.3614
更新日期:1989-09-01 00:00:00
abstract::An electrophoretic mobility shift assay was used to characterize interactions of nuclear proteins with a DNA segment in the enhancer element of the leukemogenic murine retrovirus SL3-3. Mutation of a DNA sequence of the 5'-TGTGG-3' type decreased transcription in vivo specifically in T-lymphocyte cell lines. Extracts ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.4.1625
更新日期:1988-04-01 00:00:00
abstract::Poly(A)-binding protein (PABP) stimulates translation initiation by binding simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation factor 4G (eIF4G). PABP activity is regulated by PABP-interacting (Paip) proteins. Paip1 binds PABP and stimulates translation by an unknown mechanism. Here, we desc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00738-08
更新日期:2008-11-01 00:00:00
abstract::Prostaglandins, pleiotropic immune modulators that induce protein kinase A (PKA), inhibit gamma interferon induction of class II major histocompatibility complex (MHC) genes. We show that phosphorylation of CIITA by PKA accounts for this inhibition. Treatment with prostaglandin E or 8-bromo-cyclic AMP or transfection ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.14.4626-4635.2001
更新日期:2001-07-01 00:00:00
abstract::Thrombin stimulation of platelets induces a transient increase in the specific activity of pp60c-src followed by a redistribution of pp60c-src to the Triton X-100-insoluble, cytoskeleton-rich fraction. Concomitant with the observed increase in pp60c-src activity was a rapid dephosphorylation of tyrosine 527 in 10 to 1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1863
更新日期:1993-03-01 00:00:00
abstract::There are three mechanisms of transcriptional repression in eukaryotes. The first is quenching, whereby repressors and activators co-occupy closely linked sites and then the repressor inhibits adjacent activators. The second is direct repression, in which repressors block the function of the core transcription complex...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.11.3990-3999.2003
更新日期:2003-06-01 00:00:00
abstract::Two cis-regulatory regions are required for efficient mRNA 3'-end processing of the maize 27-kDa zein mRNA: a region containing a duplicated AAUGAA poly(A) signal and a region that is present upstream from it. Strict spatial positioning of these two regions is required for efficient mRNA 3'-end processing. Insertion o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.10.6829
更新日期:1994-10-01 00:00:00
abstract::Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug resistance. Here, we defined the targets and mechanisms of ant...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.6.4101
更新日期:1999-06-01 00:00:00
abstract::A retroviral vector system was developed to study the retrotransposition of RNAs lacking all cis-acting sequences required for normal retroviral replication. Our experiments indicate that such RNAs can be encapsidated in retroviral proteins, reverse transcribed, and integrated to form functional cDNA genes in infected...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.6.2328
更新日期:1988-06-01 00:00:00
abstract::The tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated by lipopolysaccharide (LPS). Here, we show that extracellular signal-regulated kinase (ERK) kinase activity but not calcineurin phosphatase activity is required for LPS-stimulated TNF-alpha gene expression. In LPS-stimulated macrophages, the ERK sub...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.16.6084-6094.2000
更新日期:2000-08-01 00:00:00
abstract::The carcinoembryonic antigen (CEA) family consists of a large group of evolutionarily divergent glycoproteins. The secreted pregnancy-specific glycoproteins constitute a subgroup within the CEA family. They are predominantly expressed in trophoblast cells throughout placental development and are essential for a positi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.19.7140-7145.2000
更新日期:2000-10-01 00:00:00
abstract::Autoimmune diseases are characterized by spontaneously occurring autoantibodies which have proven to be useful reagents for the characterization of specific nuclear proteins. Using a monoclonal autoantibody (72B9) derived from a murine lupus strain, we have cloned a cDNA from the human T-cell line MOLT-4, which encode...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.5.2164
更新日期:1990-05-01 00:00:00
abstract::XPC is responsible for DNA damage sensing in nucleotide excision repair (NER). Mutations in XPC lead to a defect in NER and to xeroderma pigmentosum (XP-C). Here, we analyzed the biochemical properties behind mutations found within three patients: one amino acid substitution (P334H, XP1MI, and GM02096), one amino acid...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00781-08
更新日期:2008-12-01 00:00:00
abstract::TGF-alpha-PE40 is a hybrid protein composed of transforming growth factor-alpha (TGF-alpha) fused to a 40,000-dalton segment of Pseudomonas exotoxin A (PE40). This hybrid protein possesses the receptor-binding activity of TGF-alpha and the cell-killing properties of PE40. These properties enable TGF-alpha-PE40 to bind...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.7.2860
更新日期:1989-07-01 00:00:00
abstract::Five mouse alpha-tubulin isotypes are described, each distinguished by the presence of unique amino acid substitutions within the coding region. Most, though not all of these isotype-specific amino acids, are clustered at the carboxy terminus. One of the alpha-tubulin isotypes described is expressed exclusively in tes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2409
更新日期:1986-07-01 00:00:00
abstract::DNA elements with the CC(A/T)6GG, or CArG, motif occur in promoters that are under different regulatory controls. CArG elements from the skeletal actin, c-fos, and myogenin genes were tested for their abilities to confer tissue-specific expression on reporter genes when the individual elements were situated immediatel...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.12.6296
更新日期:1991-12-01 00:00:00
abstract::A prominent hallmark of most human cancer is aneuploidy, which is a result of the chromosomal instability of cancer cells and is thought to contribute to the initiation and progression of most carcinomas. The developmentally regulated GATA6 transcription factor is commonly lost in ovarian cancer, and the loss of its e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00087-09
更新日期:2009-09-01 00:00:00
abstract::Plk is a mammalian serine/threonine protein kinase whose activity peaks at the onset of M phase. It is closely related to other mammalian kinases, Snk, Fnk, and Prk, as well as to Xenopus laevis Plx1, Drosophila melanogaster polo, Schizosaccharomyces pombe Plo1, and Saccharomyces cerevisiae Cdc5. The M phase of the ce...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.6.3408
更新日期:1997-06-01 00:00:00
abstract::In a previous paper, we have shown that in the absence of stress, mouse embryonal carcinoma cells, like mouse early embryo multipotent cells, synthesize high levels of 89- and 70-kilodalton heat shock proteins (HSP)(O. Bensaude and M. Morange, EMBO J. 2:173-177, 1983). We report here the pattern of proteins synthesize...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.4.730
更新日期:1984-04-01 00:00:00
abstract::Minisatellite DNA is repetitive DNA with a repeat unit length from 15 to 100 bp. While stable during mitosis, it destabilizes during meiosis, altering both in length and in sequence composition. The basis for this instability is unknown. To investigate the factors controlling minisatellite stability, a minisatellite s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.3.953-964.2002
更新日期:2002-02-01 00:00:00
abstract::Although the U1 small nuclear ribonucleoprotein particle (snRNP) was the first mRNA-splicing cofactor to be identified, the manner in which it functions in splicing is not precisely understood. Among the information required to understand how U1 snRNP participates in splicing, it will be necessary to know its structur...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.11.4030
更新日期:1987-11-01 00:00:00
abstract::The antimetabolite 5-fluorouracil (5FU) is a widely used chemotherapeutic for the treatment of solid tumors. Although 5FU slows DNA synthesis by inhibiting the ability of thymidylate synthetase to produce dTMP, the drug also has significant effects on RNA metabolism. Recent genome-wide assays for 5FU-induced haploinsu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.24.10766-10776.2004
更新日期:2004-12-01 00:00:00
abstract::Transcription from the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) is inhibited in murine stem cells and induced during maturation of these cells. We have investigated whether alterations in the activity of this viral regulatory element also occur during differentiation of human myeloid leukemia...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.8.3571
更新日期:1989-08-01 00:00:00
abstract::EYA1 is known to be overexpressed in human breast cancer, in which the Myc protein is also accumulated in association with decreased phospho-T58 (pT58) levels. We have recently reported that EYA1 functions as a unique protein phosphatase to dephosphorylate Myc at pT58 to regulate Myc levels. However, it remains unclea...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00499-16
更新日期:2016-12-19 00:00:00
abstract::In resting cells, the NFAT1 transcription factor is kept inactive in the cytoplasm by phosphorylation on multiple serine residues. These phosphorylated residues are primarily contained within two types of serine-rich motifs, the SRR-1 and SP motifs, which are conserved within the NFAT family. Several different kinases...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.10.4184-4195.2004
更新日期:2004-05-01 00:00:00
abstract::In selective autophagy, the adaptor protein SQSTM1/p62 plays a critical role in recognizing/loading cargo (e.g., malfolded proteins) into autophagosomes for lysosomal degradation. Here we report that whereas SQSTM1/p62 levels fluctuated in a time-dependent manner during autophagy, inhibition or knockdown of Cdk9/cycli...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01383-13
更新日期:2014-09-15 00:00:00
abstract::Binding of the thyroid hormone receptor (TR) to thyroid hormone-responsive elements (TREs) is crucial for regulation of gene expression by thyroid hormone. The TR binds to each half-site of a palindromic TRE separately, as a monomer, or simultaneously, as a homodimer. In addition, the TR monomer interacts with a 42-kD...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5005
更新日期:1991-10-01 00:00:00
abstract::Mitochondria are indispensable organelles implicated in multiple aspects of cellular processes, including tumorigenesis. Heat shock proteins play a critical regulatory role in accurately delivering the nucleus-encoded proteins through membrane-bound presequence translocase (Tim23 complex) machinery. Although altered e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01527-13
更新日期:2014-05-01 00:00:00
abstract::Leukemia results from the expansion of self-renewing hematopoietic cells that are thought to contain mutations that contribute to disease initiation and progression. Studies of the gene expression profiles of human acute myeloid leukemia samples has allowed their classification based on the presence of translocations ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.24.10882-10893.2004
更新日期:2004-12-01 00:00:00
abstract::SATB1 is expressed primarily in thymocytes and orchestrates temporal and spatial expression of a large number of genes in the T-cell lineage. SATB1 binds to the bases of chromatin loop domains in vivo, recognizing a special DNA context with strong base-unpairing propensity. The majority of thymocytes are eliminated by...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.16.5591-5604.2001
更新日期:2001-08-01 00:00:00