Transcriptional activator stimulation

Deng, T. and M. Karin. c-Fos transcriptional activity stimulated by H-ras-activated protein kinase distinct from JNK and ERK. Nature 371 171-175, 1994. 

TBP mutants lacking the N-terminal region are fully functional in promoter binding and stimulation of basal transcription and therefore these two functions must be provided by the C-terminal domain. Furthermore, the C-terminal domain of yeast TBP contains all the functions essential for normal yeast cell growth and for responses to specific transcriptional activators with a net negative charge. This C-terminal domain contains two homologous... 

The formation of the PIC described above is based on the sequential addition of purified components in in vitro experiments. An essential feature of this model is that the assembly takes place on the DNA template. Accordingly, transcription activators, which have autonomous DNA binding and activation domains (see Chapter 39), are thought to function by stimulating either PIC formation or PIC function. The TAF coactivators are viewed as bridging factors that communicate between the upstream activators, the proteins associated with pol II, or the many other components of TFIID. This view, which assumes that there is stepwise assembly of the PIC—promoted by various interactions between activators, coactivators, and PIC components— is illustrated in panel A of Figure 37-10. This model was supported by observations that many of these proteins could indeed bind to one another in vitro. 

RAJAVASHISTH T B, YAMADA H and MiSHRA N K (1995) Transcriptional activation of macrophage stimulating factor gene by minimally modified LDL Arteriosclerosis, Thrombosis and Vascular Biology 15, 1591-8. 

Figure 5.1. Yeast two-hybrid system. Interaction of proteins X and Y upstream of a reporter gene leads to transcriptional activation. Protein X is part of a fusion protein that binds to a site on DNA upstream of the reporter gene by means of a DNA binding domain. Protein Y is part of a fusion protein that contains a transcriptional activation domain. Interaction of proteins X and Y places the activation domain in the vicinity of the reporter gene and stimulates its transcription.

Stimulation of a cell by first messengers that increase cellular Ca2+ concentrations similarly activates CREB (Fig. 23-9). This appears to occur via the phosphorylation of CREB on serine 133 by a CaMK, probably CaMKIV as well as, possibly, CaMKI. It remains to be established whether the activated kinase translocates to the nucleus, by analogy with the catalytic subunit of the cAMP kinase, or whether elevated Ca2+ signals enter the nucleus and activate the kinase already there. Interestingly, phosphorylation of CREB on a distinct serine residue, serine 142, by CaMKII appears to inhibit the transcriptional activity of CREB in vitro, although whether this inhibitory effect occurs in vivo is unknown. 

Recently, a Japanese research group published preclinical safety and efficacy data of an oral antiestrogen (TZE-5323) (Saito et al. 2003). This drug has been shown to have a strong affinity for human ERa and ER/i and a dose-dependent capacity to inhibit estradiol-stimulated transcriptional activation (Saito et al. 2003). In the experimental endometriosis model in rats, TZE-5323 dose-dependently reduced the volume of the endometrial implant with an effectiveness similar to that of danazol and leuprorelin acetate without causing significant changes in bone mineral density and in serum estradiol levels (Saito et al. 2003). 

The interaction of CSN5 to the member of the IkB multigene family Bcl3, the progesterone receptor PR, and the steroid receptor co-activator SRC-1, leads to stabilization of Bcl3-p50 and PR-SRC-1 complexes and enhances transcriptional activity [42, 43]. Whereas AP-1 activity is stimulated by interaction of CSN5 with the integrin adhesion receptor LFA-1 [44], the opposite effect was reported in the... 

Figure 3. (a) Scheme of transcription, (b) Histone chaperone nucleophosmin/NPMl enhance acetylation dependent chromatin transcription NPMl stimulates chromatin transcription in a dose dependent manner. Lane 1,without activator lanes 2-6, with the activator Gal-VP16 (50 ng) lanes 3-6, with p300 (25 ng) lanes 4-6, with acetyl CoA (1.5 pM) lane 5, 1 pmol, lane 6, 10 pmols of full length NPMl... 

Transcriptional activator A protein which activates (up regulates) transcription of a specific gene or group of genes. Transcriptional activators are DNA binding proteins which usually bind to specific sequences close to the promoter and enhance the binding of RNA polymerase and/or stimulate the rate of transcription... 

Laurent, B.C., Treich, I., and Carlson, M. (1993) The yeast SNF2/SWI2 protein has DNA-stimulated ATPase activity required for transcriptional activation. Genes Dev. 7, 583-591. 

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