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: 33.12). 11/2006; 127(2):261-4. DOI: 10.1016/j.cell.2006.10.002
Source: PubMed

ABSTRACT 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.
    Biochimica et Biophysica Acta 06/2013; 1833(10). DOI:10.1016/j.bbamcr.2013.05.023 · 4.66 Impact Factor
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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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    ABSTRACT: The transcriptional activator WRKY45 plays a major role in the salicylic acid (SA)/benzothiadiazole-induced defense program in rice. Here, we show that the nuclear ubiquitin proteasome system (UPS) plays a role in regulating the function of WRKY45. Proteasome inhibitors induced accumulation of polyubiquitinated WRKY45 and transient upregulation of WRKY45 target genes in rice cells, suggesting that WRKY45 is constantly degraded by the UPS to suppress defense responses in the absence of defense signals. Mutational analysis of the nuclear localization signal (NLS) indicated that UPS-dependent WRKY45 degradation occurs in the nuclei. Interestingly, transcriptional activity of WRKY45 after SA treatment was impaired by proteasome inhibition. The same C-terminal region in WRKY45 was essential for both transcriptional activity and UPS-dependent degradation. These results suggest that UPS regulation also plays a role in transcriptional activity of WRKY45. It has been reported that AtNPR1, the central regulator of the SA pathway in Arabidopsis, is regulated by the UPS. We found that OsNPR1/NH1, the rice counterpart of NPR1, was not stabilized by proteasome inhibition under an uninfected condition. We discuss the differences in the post-translational regulation of the SA-pathway components between rice and Arabidopsis. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.
    The Plant Journal 09/2012; 73(2). DOI:10.1111/tpj.12035 · 6.82 Impact Factor
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    • "Importantly, failure to phosphorylate and thus degrade NPR1 abolished the expression of direct target genes, indicating that NPR1 coactivator instability is intimately linked to its ability to initiate transcription. Similar scenarios in which (co)activator destruction is necessary for gene activation have been uncovered in yeast and mammalian cells (Collins and Tansey, 2006; Kodadek et al., 2006; Spoel et al., 2010). In fact, many transcription activators contain overlapping sequences that activate transcription and signal for their degradation (Salghetti et al., 2000). "
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    ABSTRACT: Plant cells maintain sophisticated gene transcription programs to regulate their development, communication, and response to the environment. Environmental stress cues, such as pathogen encounter, lead to dramatic reprogramming of transcription to favor stress responses over normal cellular functions. Transcription reprogramming is conferred by the concerted action of myriad transcription (co)factors that function directly or indirectly to recruit or release RNA Polymerase II. To establish an effective defense response, cells require transcription (co)factors to deploy their activity rapidly, transiently, spatially, and hierarchically. Recent findings suggest that in plant immunity these requirements are met by posttranslational modifications that accurately regulate transcription (co)factor activity as well as by sequential pulse activation of specific gene transcription programs that provide feedback and feedforward properties to the defense gene network. Here, we integrate these recent findings from plant defense studies into the emerging field of transcription dynamics in eukaryotes.
    The Plant Cell 08/2011; 23(8):2809-20. DOI:10.1105/tpc.111.087346 · 9.58 Impact Factor


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