Transactivating domain

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. 

N-terminal domain is the least conserved region and contains the transactivation domain AF-1. 

The other transactivator domain, TAF2, is found immersed in the LBD and acts only when the hormone-receptor complex is formed. A sequence of 15 well-conserved amino acids from the different members of the family of nuclear receptors, and situated very close to the carboxyl end of the receptors, participates in it (Gruber et al. 2002 Nilsson et al. 2001). 

The transactivation domains only make their accessibility evident in the dimer bound to the HRE. It is very probable that, in this way, the spatial structure (tertiary) optimizes itself so that the contact surfaces between the receptor and the other cofactors of transcription are formed. 

Chemoenzymatic Synthesis of a Characteristic Glyco-phosphopeptide from the Transactivation Domain of the Serum Response Factor, J. Sander H. Waldmann, Angew. Chem 1999, 111, 1337-1339, Angew. Chem Int. Ed. 1999,38,1250-1252... 

Moeett, E. and P. Boek, A novel transactivation domain in parkin. Trends Biochem Sci, 1999, 24(6), 229-31. 

The absence of a transactivation-competent NF-kB heterodimer in the nucleus of latently infected resting memory CD4+ T cells could contribute to latency. Activation of the NF-kB pathway leading to migration of a transactivating heterodimer such as p50/p65 could allow viral reactivation. In the absence of induction, NF-kB p50-HDACl complexes constitutively bind the latent HIV-1 LTR (Williams et al, 2006). NF-kB p50 does not possess a transactivation domain. These p50-HDACl complexes induce histone deacetylation and repressive changes in chromatin structure of the HIV-1 LTR (Williams et al, 2006). Knockdown of p50 expression reduces HDACl binding to the latent HIV-1 LTR and induces RNA polymerase II recruitment (Williams et al, 2006). Concomitantly with HIV-1 transcriptional activation, the p65 subunit and different HATs are recruited to the viral promoter (Lusic et al, 2003 Thierry et al, 2004). 

The LEDs of the ERa and the ER/1 share a similar overall architecture. Two separate transactivation domains (AF) mediate the transactivation of the ER an N-terminal hgand-independent activation fimction (AF-1) and a C-terminal ligand-dependent activation function (AF-2), which is located within the LED (Fig. 3). The surface of the AF-1 is composed of amino acids in helices 3,4, 5 and 12, and the binding of ligands alters the position of heHx... 

Fig. 1.21. Structural and functional principles of transcription activators. Typical transcription activators of encaryotes possess a DNA-binding domain, an effector domain and a transactivating domain. An incoming signal is registered by the effector domain and transformed into a change in affinity for DNA. In the active state, the transcription activator is capable of binding to its cognate DNA-binding element. Protein-protein interactions with the transcription apparatus bound to the promoter mediate a stimnlation of transcription initiation.

The JNK/SAPK proteins bind to the N-terminal transactivation domain of c-Jun protein and phosphorylate the residues Ser63 and Ser73. Consequently, increased transcription activity is observed of genes controlled by c-Jim. 

In the N-terminal region of p53, there is a transactivation domain which p53 uses to make contact with the transcription apparatus. Different protein binding sites have been identified in this region. These include binding sites for components of the TFIID complex and for coactivators such as the CBP/p300 coactivator (see 1.4.6). 

Li W, Yu SW, Kong AN. 2006. Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain. J Biol Chem 281 27251-27263. 

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