Keeping Transcriptional Activators under Control

Department of Internal Medicine , University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390, USA.
Cell (Impact Factor: 32.24). 11/2006; 127(2):261-4. DOI: 10.1016/j.cell.2006.10.002
Source: PubMed


Transcriptional activators need to be modulated and eventually switched off after the initial event that triggers their activation. Here, we discuss how ubiquitination of activators and their proteasome-mediated turnover are crucial steps in this process.

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    • "Interestingly, it has been known for years that the UPS is involved in transcription — in a proteolytic as well as a non-proteolytic manner ([84] and references therein). The UPS controls the function of transcriptional activators mainly by degradation [84] [85]. Its most prominent function, however, is probably the regulation of gene activity by ubiquitylation of histones in a non-proteolytic manner [86] [87]. "
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    ABSTRACT: The conserved Prp19 complex (Prp19C) - also known as NineTeen Complex (NTC) -functions in several processes of paramount importance for cellular homeostasis. NTC/Prp19C was discovered as a complex that functions in splicing and more specifically during the catalytic activation of the spliceosome. More recent work revealed that NTC/Prp19C plays a role in transcription elongation in S. cerevisiae and in genome maintenance in higher eukaryotes. In addition, mouse PRP19 might ubiquitylate proteins targeted for degradation and guide them to the proteasome. Furthermore, NTC/Prp19C has been implicated in lipid droplet biogenesis. In the future, the molecular function of NTC/Prp19C in all of these processes needs to be refined or elucidated. Most of NTC/Prp19C's functions have been shown in only one or few organisms. However, since this complex is highly conserved it is likely that it has the same functions across all species. Moreover, one NTC/Prp19C or different subcomplexes could function in the above-mentioned processes. Intriguingly, NTC/Prp19C might link these different processes to ensure an optimal coordination of cellular processes. Thus, many important questions about the functions of this interesting complex remain to be investigated. In this review we discuss the different functions of NTC/Prp19C focusing on the novel and emerging ones as well as open questions.
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    • "Rescue of AQP5 mRNA expression by proteasome inhibitors (Fig. 8 E–G) suggests that they are regulating a transcription factor. Many critical transcriptional factors are maintained at appropriate levels by targeted ubiquitination and degradation via the 26S proteasome (complete complex) [54], [56]. It is possible that the proteasome dependent mechanism transduces the hypoxic stress signal to AQP5 by degradation of an inhibitor(s) of its transcriptional repressors, thus resulting in decreased transcription of AQP5. "
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    • "In some cases, UPS-dependent degradation of a transcription factor is required for its full activity as a transcriptional activator (Kodadek et al., 2006). To investigate the relationship between transcriptional activity and UPS-dependent degradation of WRKY45, we generated a deletion series of the WRKY45 coding sequence and examined their transcriptional activity and protein degradation. "
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