Transgenic overexpression of HSP56 does not result in cardiac hypertrophy nor protect from ischaemia/reperfusion injury.

Heat shock proteins are known to be induced during and following different forms of cardiac stress. It has previously been shown that their expression is beneficial for the heart following trauma such as ischaemia-reperfusion (I/R) injury. Heat shock protein 56 (HSP56) belongs to the family of FK506-binding immunophilin proteins and is found in steroid receptor complexes, notably the glucocorticoid receptor.

Arginine residues are important in determining the binding of human monoclonal antiphospholipid antibodies to clinically relevant antigens.

In the antiphospholipid syndrome (APS), antiphospholipid Abs (aPL) bind to anionic phospholipids (PL) and various associated proteins, especially beta(2)-glycoprotein I (beta2GPI) and prothrombin. In the present study, we show that altering specific Arg residues in the H chain of a human pathogenic beta2GPI-dependent aPL, IS4, has major effects on its ability to bind these clinically important Ags. We expressed whole human IgG in vitro by stable transfection of Chinese hamster ovary cells with expression plasmids containing different V(H) and V(L) sequences.

The Brn-3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells.

The Brn-3b transcription factor has been shown to be overexpressed in human breast cancer cells and contributes toward cell growth regulation. Using micro-arrays, more than 50 cancer-related genes regulated by Brn-3b in human breast cancer cells have been identified. For example, Brn-3b activates the cell cycle regulator CDK4 that provides a mechanism by which Brn-3b controls the growth of breast cancer cells.

Phosphorylation of the Brn-3a transcription factor is modulated during differentiation and regulates its functional activity.

Brn-3a is a transcription factor expressed in a subset of neurons of the peripheral nervous system. Its role encompasses the activation of genes involved in neuronal differentiation and survival. While a lot of data have been produced on Brn-3a target promoters, very little is known about the upstream regulatory signals that mediate its activation in response to differentiation.

Expression of the Brn-3b transcription factor correlates with expression of HSP-27 in breast cancer biopsies and is required for maximal activation of the HSP-27 promoter.

In breast cancer, overexpression of the small heat shock protein, HSP-27, is associated with increased anchorage-independent growth, increased invasiveness, and resistance to chemotherapeutic drugs and is associated with poor prognosis and reduced disease-free survival. Therefore, factors that increase the expression of HSP-27 in breast cancer are likely to affect the prognosis and outcome of treatment. In this study, we show a strong correlation between elevated levels of the Brn-3b POU transcription factor and high levels of HSP-27 protein in manipulated MCF-7 breast cancer cells as well as in human breast biopsies.

Reduction in endogenous parkin levels renders glial cells sensitive to both caspase-dependent and caspase-independent cell death.

Mutations in the parkin gene give rise to a familial form of Parkinson's disease, autosomal recessive juvenile Parkinsonism (AR-JP). Although the exact mechanisms are unclear, it is thought that these 'loss-of-function' mutations contribute to the pathological process by interfering with parkin's E3 ubiquitin ligase activity. In order to mimic the in vivo loss-of-function, we produced tet-inducible glial cell lines that, in the presence of doxycycline, were able either to under- or to over-express the parkin protein.

Distinct domains of Brn-3a regulate apoptosis and neurite outgrowth in vivo.

The Brn-3a transcription factor is critical for the normal development of the nervous system, promoting both neuronal survival and neurite outgrowth. By manipulating the Brn-3a gene in intact mice, we show that these two functions are separately controlled with an N-terminal domain being essential for neuronal survival, whereas the POU domain is essential for neurite outgrowth. Hence the two naturally occurring forms of Brn-3a, which either contain or lack the N-terminal domain, are likely to play distinct roles in the nervous system.

The transcriptional co-activators CBP and p300 are activated via phenylephrine through the p42/p44 MAPK cascade.

The CBP and p300 co-activators play a key role in many aspects of gene regulation being recruited to the DNA via transcription factors that are targets for specific signaling pathways. It has previously been demonstrated that in neuronal cells the ability of CBP and p300 to activate transcription can be directly stimulated by nerve growth factor or calcium-activated signaling pathways. Here we demonstrate that, in cardiac cells, the activity of CBP and p300 is stimulated by phenylephrine (PE) treatment and that they are required for the activation of atrial naturetic factor (ANF) gene expression by PE.