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Notch1 genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch1 signaling in osteogenesis is not well defined. Notch1 controls osteoblast differentiation by affecting Runx2, but the question arises whether normal osteoblastic differentiation can occur regardless of the presence of Notch1. In this study, we observed the downregulation of Notch1 signaling during osteoblastic differentiation. BMPR-IB/Alk6-induced Runx2 proteins reduced Notch1 activity to a marked degree. Accumulated Runx2 suppressed Notch1 transcriptional activity by dissociating the Notch1-IC-RBP-Jk complex. Using deletion mutants, we also determined that the N-terminal domain of Runx2 was crucial to the binding and inhibition of the N-terminus of the Notch1 intracellular domain. Notably, upregulation of the Runx2 protein level paralleled reduced expression of Hes1, which is a downstream target of Notch1, during osteoblast differentiation. Collectively, our data suggest that Runx2 is an inhibitor of the Notch1 signaling pathway during normal osteoblast differentiation. © 2011 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The past two decades have witnessed an important shift in the historiography of the Society of Jesus. The older style of Jesuit history, flavoured with confessional polemics, and so often dependent on the work of Jesuit scholars isolated from the more secularly oriented academic community, had already ceased to dominate when John O'Malley's magisterial The First Jesuits appeared in 1993. 1 Since then, the partnering of Jesuit and non-Jesuit scholars has produced scholarship that is generally sympathetic to the Society's aims and methods while avoiding neither criticism of the Jesuits nor thorough, judicious use of archival materials. The significance of this trend is heightened by the declining numbers of Jesuits in North America and Europe, creating a situation where the advancement of Jesuit studies will, at least in these venues, increasingly become the responsibility of non-Jesuits. With the passing of the Jesuit scholar of Jesuits, something is lost and gained; potentially greater objectivity towards the Society is offset by the loss of insight into the individual and corporate experience of being a Jesuit. The four books reviewed here illustrate in varying degrees these developments in the field. [ABSTRACT FROM AUTHOR]

Protein phosphorylation represents one of the major mechanisms for transcription factor activation. Here we demonstrate a molecular mechanism by which phosphorylation by mitogen-activated protein (MAP) kinases leads to changes in transcription factor activity. MAP kinases stimulate DNA binding and transcriptional activation mediated by the mammalian ETS-domain transcription factor Elk-1. Phosphorylation of the C-terminal transcriptional activation domain induces a conformational change in Elk-1, which accompanies the stimulation of DNA binding. C-terminal phosphorylation is coupled to activation of DNA binding by the N-terminal DNA-binding domain via all additional intermediary domain. Activation of DNA binding is mediated by all allosteric mechanism involving the key phosphoacceptor residues. Together, these results provide a molecular model for how phosphorylation induces changes in Elk-1 activity. [ABSTRACT FROM AUTHOR]

The MADS-box family of transcription factors has been defined on the basis of primary sequence similarity amongst numerous proteins from a diverse range of eukaryotic organisms including yeasts, plants, insects, amphibians and mammals. The MADS-box is a conserved motif found within the DNAbinding domains of these proteins and the name refers to four of the originally identified members: MCM1, AG, DEFA and SRF. Several proteins within this family have significant biological roles. For example, the human serum-response factor (SRF) is involved in co-ordinating transcription of the protooncogene c-fos, whilst MCM1 is central to the transcriptional control of cell-type specific genes and the pheromone response in the yeast Saccharomyces cerevisiae. The RSRF/MEF2 proteins comprise a subfamily of this class of transcription factors which are key components in muscle-specific gene regulation. Moreover, in plants, MADS-box proteins such as AG, DEFA and GLO play fundamental roles during flower development. The MADS-box is a contiguous conserved sequence of 56 amino acids, of which 9 are identical in all family members described so far. Several members have been shown to form dimers and consequently two functional regions within the MADS-box have been defined. The N-terminal half is the major determinant of DNA-binding specificity whilst the C-terminal half is necessary for dimerisation. This organisation allows the potential formation of numerous proteins, with subtly different DNA-binding specificities, from a limited number of genes by heterodimerisation between different MADS-box proteins. The majority of MADS-box proteins bind similar sites based on the consensus sequence CC(A/T)6GG although each protein apparently possesses a distinct binding specificity. Moreover, several MADS-box proteins specifically recruit other transcription factors into multi-component regulatory complexes. Such interactions with tither proteins appears to be a common theme within this family and play a pivotal role in the regulation of target genes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Religious and Secular Death: A Parting of the Ways" by N. Tonti-Filippini.