Artificial Transcriptional Activation Domains

Lum, Jenifer K.; Mapp, Anna K.

doi:10.1002/cbic.200500036

Cited by 10 publications

(17 citation statements)

References 52 publications

(49 reference statements)

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“…Transition metal complexes represent an important class of compounds with great potential for therapeutic interventions [4]. Nucleic acids are often the target for many chemotherapeutic drugs especially anti-tumor drugs [4][5][6][7][8][9][10][11][12]. For example, cisplatin (cis-[(NH 3 ) 2 PtCl 2 ]), a widely used anticancer agent, functions by cross-linking DNA strands through coordination of nucleic acid bases [2].…”

Section: Introductionmentioning

confidence: 99%

Iron(III)-salen damages DNA and induces apoptosis in human cell via mitochondrial pathway

Woldemariam

Mandal

2008

Journal of Inorganic Biochemistry

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Section: Introductionmentioning

confidence: 99%

Iron(III)-salen damages DNA and induces apoptosis in human cell via mitochondrial pathway

Woldemariam

Mandal

2008

Journal of Inorganic Biochemistry

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“…Anna K. Mapp (University of Michigan, Ann Arbor) receives the award for her work on the role small molecules play in gene transcription, and in particular on artificial transcription activation domains 2a. Her group uses synthetic organic chemistry to understand how genes are regulated, and the role of protein interactions in gene activation.…”

Section: Awarded…︁mentioning

confidence: 99%

Organometallic Chemistry: Oro Honored / Biological Chemistry: Mapp Awarded / Organic Chemistry: Prize for Gooßen

2008

Angew Chem Int Ed

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“…Other transactivating domains include VP16, Gal4 and c-Myb, respectively originating from herpes simplex virus, yeast and humans. Synthetic transactivation domains have also been created, using acidrich peptides or polar and hydrophobic small molecules [58].…”

Section: Scaffold Proteins Zinc-finger Proteins and Synthetic Transmentioning

confidence: 99%

Computer-aided design of modular protein devices: Boolean AND gene activation

Salis

Kaznessis

2006

Phys. Biol.

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Many potentially useful synthetic gene networks require the expression of an engineered gene if and only if two different DNA-binding proteins exist in sufficient concentration. While some natural and engineered systems activate gene expression according to a logical AND-like behavior, they often utilize allosteric or cooperative protein-protein interactions, rendering their components unsuitable for a toolbox of modular parts for use in multiple applications. Here, we develop a quantitative model to demonstrate that a small system of interacting fusion proteins, called a protein device, can activate an engineered gene according to the Boolean AND behavior while using only modular protein domains and DNA sites. The fusion proteins are created from transactivating, DNA-binding, non-DNA binding, and protein-protein interaction domains along with the corresponding peptide ligands. Using a combined kinetic and thermodynamic model, we identify the characteristics of the molecular components and their rates of constitutive production that maximize the fidelity of AND behavior. These AND protein devices facilitate the creation of complex genetic programs and may be used to create gene therapies, biosensors and other biomedical and biotechnological applications that turn on gene expression only when multiple DNA-binding proteins are simultaneously present.

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Artificial Transcriptional Activation Domains

Cited by 10 publications

References 52 publications

Iron(III)-salen damages DNA and induces apoptosis in human cell via mitochondrial pathway

Iron(III)-salen damages DNA and induces apoptosis in human cell via mitochondrial pathway

Organometallic Chemistry: Oro Honored / Biological Chemistry: Mapp Awarded / Organic Chemistry: Prize for Gooßen

Computer-aided design of modular protein devices: Boolean AND gene activation

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