Transcription factor

About: Transcription factor is a research topic. Over the lifetime, 82881 publications have been published within this topic receiving 5400448 citations. The topic is also known as: transcription factors.

Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins.

Abstract: BH3-only proteins are structurally distant members of the Bcl-2 protein family that trigger apoptosis. Genetic experiments have shown that these proteins are essential initiators of programmed cell death in species as distantly related as mice and C. elegans. BH3-only proteins share with each other and with the remainder of the Bcl-2 family only a nine amino acid BH3 (Bcl-2 Homology) region. Mutational analyses have demonstrated that this domain is required for their ability to bind to Bcl-2-like pro-survival proteins and to initiate apoptosis. So far only one BH3-only protein, EGL-1, has been identified in C. elegans and it is required for all developmentally programmed death of somatic cells in this species. In contrast, mammals have at least 10 BH3-only proteins that differ in their expression pattern and mode of activation. Studies in gene targeted mice have indicated that different BH3-only proteins are required for the initiation of distinct apoptotic stimuli. The pro-apoptotic activities of BH3-only proteins are stringently controlled by a variety of mechanisms. C. elegans egl-1 as well as mammalian hrk/dp5, noxa, puma/bbc3 and bim/bod are regulated by a diverse range of transcription factors. Certain BH3-only proteins, including Bad, Bik/Nbk, Bid, Bim/Bod and Bmf, are restrained by post-translational modifications that cause their sequestration from pro-survival Bcl-2 family members. In this review we describe current knowledge of the functions and transcriptional as well as post-translational control mechanisms of BH3-only proteins.

Partners in transcription: NFAT and AP-1.

Abstract: Combinatorial regulation is a powerful mechanism that enables tight control of gene expression, via integration of multiple signaling pathways that induce different transcription factors required for enhanceosome assembly. The four calcium-regulated transcription factors of the NFAT family act synergistically with AP-1 (Fos/Jun) proteins on composite DNA elements which contain adjacent NFAT and AP-1 binding sites, where they form highly stable ternary complexes to regulate the expression of diverse inducible genes. Concomitant induction of NFAT and AP-1 requires concerted activation of two different signaling pathways: calcium/calcineurin, which promotes NFAT dephosphorylation, nuclear translocation and activation; and protein kinase C (PKC)/Ras, which promotes the synthesis, phosphorylation and activation of members of the Fos and Jun families of transcription factors. A fifth member of the NFAT family, NFAT5, controls the cellular response to osmotic stress, by a mechanism that requires dimer formation and is independent of calcineurin or of interaction with AP-1. Pharmacological interference with theNFAT:AP-1 interaction may be useful in selective manipulation of the immune response. Balanced activation of NFAT and AP-1 is known to be required for productive immune responses, but the role of NFAT:AP-1 interactions in other cell types and biological processes remains to be understood.

Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer

Abstract: The transcription factor Foxp3 is involved in the differentiation, function and survival of CD4+CD25+ regulatory T (Treg) cells. Details of the mechanism underlying the induction of Foxp3 expression remain unknown, because studies of the transcriptional regulation of the Foxp3 gene are limited by the small number of Treg cells in mononuclear cell populations. Here we have generated a model system for analyzing Foxp3 induction and, by using this system with primary T cells, we have identified an enhancer element in this gene. The transcription factors Smad3 and NFAT are required for activity of this Foxp3 enhancer, and both factors are essential for histone acetylation in the enhancer region and induction of Foxp3. These biochemical properties that define Foxp3 expression explain many of the effects of transforming growth factor-β on the function of Foxp3+ Treg cells.