Aminoacyl-Anthraquinones: DNA-Binding and Sequence Specificity

1990 ◽  
pp. 207-224 ◽  
Author(s):  
Manlio Palumbo ◽  
Barbara Gatto
Keyword(s):  
Dna Binding ◽  
Sequence Specificity

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

scholarly journals Multicomponent differentiation-regulated transcription factors in F9 embryonal carcinoma stem cells.

1991 ◽  
Vol 11 (3) ◽  
pp. 1686-1695 ◽  
Author(s):  
M K Shivji ◽  
N B La Thangue
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Dna Binding ◽  
Embryonal Carcinoma ◽  
Regulatory Sequence ◽  
Dependent Manner ◽  
Sequence Specificity ◽  
Dna Sequence Specificity ◽  
Cell Extracts

Murine F9 embryonal carcinoma (F9 EC) stem cells have an E1a-like transcription activity that is down-regulated as these cells differentiate to parietal endoderm. For the adenovirus E2A promoter, this activity requires at least two sequence-specific transcription factors, one that binds the cyclic AMP-responsive element (CRE) and the other, DRTF1, the DNA-binding activity of which is down-regulated as F9 EC cells differentiate. Here we report the characterization of several binding activities in F9 EC cell extracts, referred to as DRTF 1a, 1b and 1c, that recognize the DRTF1 cis-regulatory sequence (-70 to -50 region). These activities can be chromatographically separated but are not distinguishable by DNA sequence specificity. Activity 1a is a detergent-sensitive complex in which DNA binding is regulated by phosphorylation. In contrast, activities 1b and 1c are unaffected by these treatments but exist as multicomponent protein complexes even before DNA binding. Two sets of DNA-binding polypeptides, p50DR and p30DR, affinity purified from F9 EC cell extracts produce complexes 1b and 1c. Both polypeptides appear to be present in the same DNA-bound protein complex and both directly contact DNA. These affinity-purified polypeptides activate transcription in vitro in a binding-site-dependent manner. These data indicate the in F9 EC stem cells, multicomponent differentiation-regulated transcription factors contribute to the cellular E1a-like activity.

scholarly journals A plant DNA-binding protein that recognizes 5-methylcytosine residues.

1989 ◽  
Vol 9 (3) ◽  
pp. 1351-1356 ◽  
Author(s):  
D L Zhang ◽  
K C Ehrlich ◽  
P C Supakar ◽  
M Ehrlich
Keyword(s):  
Dna Binding ◽  
Dna Sequence ◽  
Base Pair ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Sequence Specificity ◽  
Dna Sequence Specificity ◽  
Plant Dna ◽  
Related Family ◽  
Nuclear Extracts

A novel, 5-methylcytosine-specific, DNA-binding protein, DBP-m, has been identified in nuclear extracts of peas. DBP-m specifically recognizes 5-methylcytosine residues in DNA without appreciable DNA sequence specificity, unlike a mammalian DNA-binding protein (MDBP), which recognizes 5-methylcytosine residues but only in a related family of 14-base-pair sequences.

Sequence-Specificity and Energy Landscapes of DNA-Binding Molecules

2011 ◽  
pp. 3-30 ◽  
Author(s):  
Joshua R. Tietjen ◽  
Leslie J. Donato ◽  
Devesh Bhimisaria ◽  
Aseem Z. Ansari
Keyword(s):  
Dna Binding ◽  
Sequence Specificity ◽  
Energy Landscapes

Transformation by Fos proteins requires a C-terminal transactivation domain

1993 ◽  
Vol 13 (12) ◽  
pp. 7429-7438
Author(s):  
R Wisdon ◽  
I M Verma
Keyword(s):  
Dna Binding ◽  
Leucine Zipper ◽  
Fibroblast Cell ◽  
Binding Activity ◽  
Sequence Specificity ◽  
Transactivation Domain ◽  
Functional Requirements ◽  
Dna Binding Activity ◽  
The Difference ◽  
Transforming Proteins

The Fos family of proteins now includes seven members: the retroviral proteins FBR-v-Fos and FBJ-v-Fos and the cellular proteins c-Fos, FosB, FosB2, Fra1, and Fra2. Four proteins (FBR-v-Fos, FBJ-v-Fos, c-Fos, and FosB) transform established rodent fibroblast cell lines, while three (FosB2, Fra1, and Fra2) do not. As all family members display sequence-specific DNA-binding activity as part of a heterodimeric complex with Jun proteins, other features must account for the differences in transforming potential. We demonstrate here that all transforming members have a C-terminal transactivation domain that is lacking in nontransforming members. The nontransforming proteins Fra1 and Fra2 can be converted to transforming proteins by fusion of a transactivation domain from either FosB or VP16. We also demonstrate that differences in the basic region-leucine zipper domain affecting either the affinity or sequence specificity of DNA binding are not determinants of the difference in transforming potential among members of the Fos family. The results further define the functional requirements for transformation by Fos proteins and suggest that the subunit composition of AP1 complexes is an important determinant of mitogenic signalling capability.

scholarly journals The Positively Charged Termini of L2 Minor Capsid Protein Required for Bovine Papillomavirus Infection Function Separately in Nuclear Import and DNA Binding

2004 ◽  
Vol 78 (24) ◽  
pp. 13447-13454 ◽  
Author(s):  
Alyson Fay ◽  
William H. Yutzy ◽  
Richard B. S. Roden ◽  
Junona Moroianu
Keyword(s):  
Dna Binding ◽  
Capsid Protein ◽  
Nuclear Import ◽  
Bovine Papillomavirus ◽  
Sequence Specificity ◽  
Viral Dna ◽  
Minor Capsid Protein ◽  
Nuclear Localization Signals ◽  
Promiscuous Dna ◽  
Positively Charged

ABSTRACT During the papillomavirus (PV) life cycle, the L2 minor capsid protein enters the nucleus twice: in the initial phase after entry of virions into cells and in the productive phase to mediate encapsidation of the newly replicated viral genome. Therefore, we investigated the interactions of the L2 protein of bovine PV type 1 (BPV1) with the nuclear import machinery and the viral DNA. We found that BPV1 L2 bound to the karyopherin α2 (Kap α2) adapter and formed a complex with Kap α2β1 heterodimers. Previous data have shown that the positively charged termini of BPV1 L2 are required for BPV1 infection after the binding of the virions to the cell surface. We determined that these BPV1 L2 termini function as nuclear localization signals (NLSs). Both the N-terminal NLS (nNLS) and the C-terminal NLS (cNLS) interacted with Kap α2, formed a complex with Kap α2β1 heterodimers, and mediated nuclear import via a Kap α2β1 pathway. Interestingly, the cNLS was also the major DNA binding site of BPV1 L2. Consistent with the promiscuous DNA encapsidation by BPV1 pseudovirions, this DNA binding occurred without nucleotide sequence specificity. Moreover, an L2 mutant encoding a scrambled version of the cNLS, which supports production of virions, rescued the DNA binding but not the Kap α2 interaction. These data support a model in which BPV1 L2 functions as an adapter between the viral DNA via the cNLS and the Kaps via the nNLS and facilitates nuclear import of the DNA during infection.

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