Transactivation mechanism

Effector caspases are activated by a transactivation mechanism, which is characterized by the catalytic action of a mature caspase on a procaspase (Thornberry et al., 1997 Earnshaw et al., 1999 Slee et al., 1999). Nevertheless, their activation can also occur by the action of other proteases. Granzyme B, a serine-protease, also has proteolytic specificity for aspartic acid residues. It is able to cleave and directly activate caspase 3 (Darmon et al., 1995). Cathepsin B, a lysosomal protease, cleaves and activates procaspase 11 (Schotte et al., 1998). 

Priming doses of a toxicant activates transactivational mechanisms of tissue repair... 

Nuclear receptors exert their different transcriptional functions through interactions with and the recruitment of co-factors to responsive promoters. Co-factors are either positive or negative regulatory proteins and are classified as co-activators, which promote, or co-repressors, which attenuate the activity of nuclear hormone receptors [46]. The molecular mechanisms that regulate the mutually exclusive interactions of the nuclear receptor with either class of co-factors have been analysed by crystallographic studies. Functional and structural studies have shown that co-activators interact with the transactivation function (AF) of nuclear hormone receptors via short, leucine-rich motifs (LXXLL) termed NR boxes , thereby transducing hormonal signals to the basal transcription machinery [47]. 

Fig. 2. Activation mechanism of caspases. Receptors convey activating signals to adapters that facilitate oligomerization and subsequent autoactivation of long prodomain caspases (I). Caspases transactivate other procaspases upon activation (11).

Transactivation of proapoptotic genes is not the only way that p53 protein can activate the apoptotic program. There is evidence that variants of p53, which are independent of Bax protein and do not operate at the transcription level, can also result in apoptosis (see Haffner and Oren, 1995 Ko and Prives, 1996). Thus, a p53-regulated redistribution of the Fas death receptor from the cytosol to the cell membrane has been demonstrated (Beimet et al., 1998). Overall, these mechanisms are poorly understood. 

The flavonoid crysin and benzothiophenes have been shown to inhibit casein kinase II (CKII), a cellular protein that may regulate HIV-1 transcription by phosphorylating (other) cellular proteins involved in the HIV-1 transcription transactivation process. This mechanism of action is independent of the nuclear factor kB-driven transcription pathway. Thus, flavonoids interfere with HIV-1 transcription and hence prevent HIV expression in latently infected cells. Their specificity and usefulness as HIV transcription inhibitors remain to be assessed. 

Shah B, Catt K. 2004. GPCR-mediated transactivation of RTKs in the CNS mechanisms and consequences. Trends Neurosci 27 48-53. 

Moriguchi Y, Matsubara H, Mori Y, Murasawa S, Masaki H, Maruyama K, Tsutsumi Y, Shibasaki Y, Tanaka Y, Nakajima T, Oda K, Iwasaka T. 1999. Angiotensin Il-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms. Circ Res 84 1073-1084. 

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