Activating transcription factor

Once the TLRs have bound their respective ligand they initiate a signalling cascade to alert the host to the presence of a threat. This signal begins with specific adapter proteins and leads to the activation of transcription factors such as NFkB, ERF-3 and IRF-7 as shown in Fig. 1. These activated transcription factors cause changes in gene expression typically leading to the production of cytokines. 

BRAND K, PAGE S, ROGLER G, BARTSCH A, BRANDL R, KNUECHEL R, PAGE M, KALTSCHMIDT C, BAEUERLE P A and NEUMEIER D (1996) Activated transcription factor NF-kB is present in the atherioscleotic lesion Journal Clinical Investigation 97, 1715-22. 

Peroxisome-proliferator activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARa is implicated in the regulation of lipid metabolism, lipoprotein synthesis, and inflammatory response in liver and other tissues. 

The mechanisms of corticosteroid receptor regulation of transcription have been elucidated. Both type I and type II corticosteroid receptors are members of a superfamily of ligand-activated transcription factors defined by protein sequence similarity. Included in this superfamily are various other steroid receptors, such as the estrogen receptor, as well as members of the retinoic acid receptor... 

ATF activating transcription factor CMR cerebral metabolic rate... 

The coupling of superantigen—major histocompatibility complex class II to T-cell receptor swifdy results in cell-signaling cascades. ° These staphylococcal toxins can increase levels of phosphatidyl inositol from quiescent T cells, such as other mitogens, as well as elicit intracellular Ca movement that activates the protein kinase C (PKC) pathway important for interleukin-2 (IL-2) expression. " IL-2 is intimately linked to T-cell proliferation. In addition to the PKC pathway, the protein tyrosine kinase (PTK) pathway is also activated by superantigens, leading to elevated expression of various proinflammatory cytokines. Staphylococcal superantigens also potently activate transcriptional factors NF-/IB (nuclear factor kappa B) and AP-1 (activator protein-1), which subsequently elicit the synthesis of proinflammatory cytokines. " " ... 

Figure 21.6 One mechanism of activation of the cell cycle by a growth factor. Binding of growth factor to its receptor activates membrane-bound phospholipase-C. This hydrolyses phosphati-dylinositol bisphosphate in the membrane to produce the messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 results in release of Ca from an intracellular store. The increased Ca + ion concentration activates protein kinases including protein kinase-C (PK-C). DAG remains membrane-bound and also activates protein kinase-C (PK-C) which remains in the activated form as it travels through the cell where it phosphory-lates and activates transcription factors. This results in activation of genes that express enzymes involved in nucleotide synthesis, DNA polymerases and cyclins, which are all reguired for the cell cycle (See Chapter 20 for provision of nucleotides and cyclins for the cell cycle).

The physiological effects of progesterone are mediated by two progesterone receptor isoforms termed PR-A and PR-E. These arise from a single gene and act as ligand-activated transcription factors to regulate the expression of... 

Fig. 1.39. Examples for families of interacting transcription factors. The circles indicate groups of eucaryotic transcription factors that can form homo- and heterodimers amongst themselves. The intersection of the circle of the ATT family with the circle of the Jun family indicates possible heterodimerization between the two famihes. The members of the Jun family can form complexes with members of the Fos family and with the members of the ATT family. The Fos family is unique in that its members can not form homodimers, but must heterodimerize with members of the Jun family. C/EBP CCAAT/enhancer binding protein ATF activating transcription factor CRE-BP cAMP responsive element binding protein. After Lamb and McKnight (1992).

Ligand-activated transcription factors are also important in embryo genesis. TCDD also causes malformations via this mechanism, as do retinoids and glucocorticoids. The importance... 

The MAPK cascade in the plant s defense against bacterial pathogens is remarkably similar to the innate immune response triggered by bacterial lipopolysac-charide and mediated by the Toll-like receptors in mammals (Fig. 12-30b). Other membrane receptors use similar mechanisms to activate a MAPK cascade, ultimately activating transcription factors and turning on the genes essential to the defense response. 

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