Trans-activating transcriptional activator

Two domains, t1 and t2, exist which affect the GR post-DNA binding transcription activity (37). The major (t1) transactivation domain is 185 amino acid residues ia length with a 58-tesidue a-heUcal functional cote (38). The t1 domain is located at the N terminus of the proteia the minor (t2) trans activation domain residues on the carboxy-terminal side of the DNA binding domain. 

The transactivation-responsive region (TAR) is located immediately downstream of the transcriptional start site in the HIV-1 LTR, encompassing nucleotides h-1 to h-59 (Berkhout et al. 1989 Muesing et al. 1987), and is reqnired for the function of the viral trans-activator protein Tat. In the absence of Tat (Fig. 5.2b), short transcripts... 

Johnston IN, Milligan ED, Wieseler-Frank J, Frank MG, Zapata V, Campisi J (2004) A role for proinflammatory cytokines and fractaUdne in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine. J Neurosci 24(33) 7353-7365 Kim YS, Panganiban AT (1993) The full-length tat protein is required for TAR-independent, post-transcriptional trans activation of human immunodeficiency virus type 1 env gene expression. J Virol 67(7) 3739-3747... 

Both MOZ and MORF have also been linked to control of transcription. In initial analyses, these MYST HATs were found to contain potent trans-activation domains in their C-termini (Champagne et al, 1999 2001). Follow-up studies demonstrated that the two proteins can indeed function as transcriptional co-activators for two Runt-domain transcription factors - Runxl and 2 (also referred to as AMLl 3) (Kitabayashi et al., 2001a Pelletier et al., 2002). Furthermore, MORF has been found in the co-activator complex associated with the peroxisome proliferator-activated receptor alpha in rat liver (Surapureddi et al., 2002). 

Toussaint, B., de Sury d Aspremont, R., Delic-Attree, 1., Berchet, V., Elsen, S., Colbeati, A., Dischert, W., Lazzaroni, Y. and Vignais, P. M. (1997) The Rhodobacter capsulatus hupSLC promoter Identification of cis-regulatory elements and of trans-activating factors involved in Hi activation of hupSLC transcription. Mol. Microbiol., 26, 927-37. 

Examples for other trans-activating domains are the glutamine rich domains of the transcription factor Spl and the prohne rich domain of the transcription factor CTF/ NFl, which contains 20 % prohne residues. 

It is assumed that trans-activating domains are structural elements that can adapt to become complementary to a smface of the transcription apparatus in a flexible and rather rmspecific manner. Information on the structure of the trans-activating domain. 

The specific transcriptional activators (see 1.4.3.1), represented by the GAL4 protein of yeast, are sequence-specific DNA-binding proteins. They possess both a DNA-binding domain and a trans-activating domain to allow them to interact directly with the transcription apparatus. 

The trans-activating domains of transcriptional activators are also common substrates for phosphorylation by protein kinases. The details by which the phosphorylation... 

Figure 2.3 Tetracycline regulated gene expression (Adapted from Applied Molecular Genetics, R.Miesfeld, Wiley publishing, New York, 1999, p. 190). Terminology CMV (cytomegalovirus) VP (activating domain of viral protein VP 16) fefR (Tet represser) tTA (tetracycline-regulated trans-activator protein) rtTA (reverse let transactivator protein) (tel())- (repeat of 7 tet operator sequences) TATA (transcription initiation consensus sequence).

Yamamoto, R., Katahira, M., Nishikawa, S., Baba, T., Taira, K. and Kumar, P.K.R. (2000) A novel RNA motif that binds efficiently and specifically to the Tat protein of HIV and inhibits the trans-activation by Tat of transcription in vitro and in vivo. Genes Cells, 5, 371-388. 

The trans-activation response (TAR) RNA is a structural motif at the 5Cend of the HIV RNA, which interacts with the Tat protein during HIV transcription. The binding site of the Tat protein is an internal loop in the TAR RNA (Fig. 15.10A). The TAR—Tat interaction assures an efficient transcription and thereby facilitates replication of the HIV virus (Frankel, 1992). Therefore, interference with the TAR—Tat interaction has been pursued as a strategy to combat HIV. Below is a description of how cw-EPR spectroscopy has yielded information about RNA dynamics that are correlated with the structure of the TAR RNA receptor bound to various ligands. 

Fig. 10.8 Above, import of the transcription factor NF-AT4 into the nucleus. In activated cells, import is initiated by calcineurin-mediated dephosphorylation of NF-AT4. Dephosphorylation unmasks the nuclear-localization signal (NLS), and at the same time blocks the nuclear export signal (NES). The NES is recognized by the exportin protein (Crml). Nuclear export is an active process. Moreover, nuclear export requires rephosphorylation of the NF-AT4 transcription factor. It is indicated that dephosphorylation by calcineurin and nuclear export are mutually exclusive, because calcineurin and Crm 1 compete for a common binding site on NES. When NES binds to Crml, NT-AT4 is exported from the nucleus, and when calcineurin binds to NES, NF-AT4 remains in the nucleus and forms a transcriptionally active complex. Below, how the extent of dephosphorylation controls the transcriptional activity of NF-AT4. When NF-AT4 is fully phosphorylated, NLS is hidden and the transcription factor remains in the cytoplasm. When NF-AT4 is only partially dephosphorylated, NLS is exposed and can interact with importin a/b which promote nuclear import, and at the same time, NES can interact with the exportin Crml, which promotes nuclear export. The consequence is that the transcription factor shuttles between the nucleus and the cytoplasm and is not transcriptionally active. In order to become transcriptionally fully active, NF-AT4 must be completely dephosphorylated. This prevents export from the nucleus by blocking NES, and may increase the affinity of the transcription factor for DNA by exposure of its trans-activating domain (TAD). (The entire scheme is reproduced with permission of Drs Patrick G. Hogan and Anjana Rao and Nature from Fig. 1 in ref. 68.)...

Tax, a transcriptional activator of the viral genome (Sodroski et al., 1984 Fujisawa et al., 1985), is a 40-kDa phosphoprotein comprised of 353 amino acids. Tax protein is the trans-activator protein, which drives viral gene expression from TRE within U3 region of LTR. Tax also interacts with cellular transcription factors such as cAMP-response element binding protein... 

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