The effect of helix-inducing constraints and downsizing upon a transcription block survival-derived functional cJun antagonist.

Inhibition of cJun is established as a promising therapeutic approach, particularly in cancer. We recently developed the "transcription block survival" (TBS) screening platform to derive functional peptide antagonists of transcription factor activity by ablating their ability to bind to cognate DNA. Using TBS, we screened a >131,000-member peptide library to select a 63-mer peptide that bound cJun and prevented 12--tetradecanoylphorbol-13-acetate response element (TRE) DNA binding.

In vitro single molecule and bulk phase studies reveal the AP-1 transcription factor cFos binds to DNA without its partner cJun.

The AP-1 transcription factor family crucially regulates progression of the cell cycle, as well as playing roles in proliferation, differentiation, and the stress response. The two best described AP-1 family members, cFos and cJun, are known to dimerize to form a functional AP-1 heterodimer that binds to a consensus response element sequence. Although cJun can also homodimerize and bind to DNA, the canonical view is that cFos cannot bind DNA without heterodimerizing with cJun.

An Approach to Derive Functional Peptide Inhibitors of Transcription Factor Activity.

We report the development of a high-throughput, intracellular "transcription block survival" (TBS) screening platform to derive functional transcription factor antagonists. TBS is demonstrated using the oncogenic transcriptional regulator cJun, with the development of antagonists that bind cJun and prevent both dimerization and, more importantly, DNA binding remaining a primary challenge. In TBS, cognate TRE sites are introduced into the coding region of the essential gene, dihydrofolate reductase (DHFR).

Selective antagonism of cJun for cancer therapy.

The activator protein-1 (AP-1) family of transcription factors modulate a diverse range of cellular signalling pathways into outputs which can be oncogenic or anti-oncogenic. The transcription of relevant genes is controlled by the cellular context, and in particular by the dimeric composition of AP-1. Here, we describe the evidence linking cJun in particular to a range of cancers.

Non-pathogenic Escherichia coli biofilms: effects of growth conditions and surface properties on structure and curli gene expression.

Biofilm formation is a harmful phenomenon in many areas, such as in industry and clinically, but offers advantages in the field of biocatalysis for the generation of robust biocatalytic platforms. In this work, we optimised growth conditions for the production of Escherichia coli biofilms by three strains (PHL644, a K-12 derivative with enhanced expression of the adhesin curli; the commercially-used strain BL21; and the probiotic Nissle 1917) on a variety of surfaces (plastics, stainless steel and PTFE). E.

Voluntary increase in latissimus dorsi muscle activity during the lat pull-down following expert instruction.

It has been observed anecdotally that while performing the multijoint lat pull-down exercise, novice strength trainers often rely on the elbow flexors to complete the movement rather than fully utilizing the relevant back muscles such as the latissimus dorsi (LD) and teres major (TM). The primary aim of the study was to determine whether specific technique instruction could result in a voluntary increase in LD and TM electromyographic (EMG) activity with a concurrent decrease in the activity of the biceps brachii (BB) during the front wide-grip lat pull-down exercise. Eight women with little or no background in strength training were asked to perform lat pull-down exercise with only basic instruction, performing 2 sets of 3 repetitions at 30% max.