Transcription factor components

The mechanistically and functionally complex N-end rule pathway (Fig. 2) is but one of many distinct pathways of the Ub system. The vast functional range of this system stems from the enormous diversity of its physiological substrates. In other words, it is the constitutive or conditional degradation of many specific proteins (cyclins, transcription factors, components of signal transduction pathways, damaged proteins) by ubiquitin-dependent pathways that underlies the involvement of the Ub system in just about every biological circuit in a living cell (5, 6, 9). 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

Instead of activating transcription the cortisol-induced GR represses IL-6 synthesis and, even more surprisingly, repression does not involve the GRE elements, but rather the kB site (Fig. 1). It appeals that of a monomeric GR protein without itself touching the DNA interacts with the RelA component of NF-kB [3]. As a result GR blocks the action of NF-kB. The negative interference by this crosstalk is not restricted to NF-kB, it occurs also with AP-1 and CREB, and with several other transcription factors not relevant for IL-6 expression. A nuclear isoform of the LIM protein Trip6 mediates the interaction between these factors and is required for the inhibitory GR function. This interesting negative crosstalk is part of the immune-suppressive action of cortisol. 

TBP binds to the TATA box in the minor groove of DNA (most transcription factors bind in the major groove) and causes an approximately 100-degree bend or kink of the DNA helix. This bending is thought to facilitate the interaction of TBP-associated factors with other components of the transcription initiation complex and possibly with factors bound to upstream elements. Although defined as a component of class II gene promoters, TBP, by virtue of its association with... 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

Figure 1. Hierarchy of control of gene expression. A total of about 50,000 to 100,000 genes are necessary to encode a mammal, most of which encode housekeeping, structural component, or terminal differentiation gene products. Transcription factor genes regulate expression of the lower-level genes and are in turn controlled by other upper-level transcription factors.

Amhros No one has looked at that directly. Ideally, one would like to monitor the phosphorylation state of different components of the signalling pathway and the status of key transcription factors, and so on. In principle this is feasible, and we would predict that we might find a cell cycle gating of one of those steps. 

Because the effects of these drugs do not occur for at least several weeks, research into mechanisms has focused on specific targets such as signaling pathways coupled to transcription factors and their target genes. Among the most studied are components of the cAMP-regulated pathways such as the... 

As explained, the immimomodulation signal starts with binding the antigen on T-cell receptor, which ultimately results in Ca2+ release. Ca2+ induces calmodulin activation, which in turn activates calcineurin, a Ca2+-dependent phosphatase. This event leads to translocation of the cytoplasmic component of the transcription factor, which is required for IL-2 gene expression and T-cell activation. 

Nelson There are three separate roles for Ca2+ waves. First, delivering Ca2+ for contraction. Second, modulating Ca2+ dependent ion channels that control the membrane potentials. Depending on the tissue this can involve BK channels, SK channels or Ca2+-activated Cl- channels. Third, controlling Ca2+-dependent transcription factors. There is quite clear evidence that the frequency and the amplitude components of the Ca2+ signals can determine which Ca2+-dependent transcription factors are activated. This can encode both short and long-term information to control smooth muscle function. 

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