TBBz but not TBBt discriminates between two molecular forms of CK2 in vivo and its implications

Zień, Piotr; Abramczyk, Olga; Domańska, K.; Bretner, Maria; Szyszka, Ryszard

doi:10.1016/j.bbrc.2003.10.165

Cited by 16 publications

(10 citation statements)

References 32 publications

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“…Conversely, yeast lacking the catalytic subunit Cka1 were approximately as resistant as wild type cells (Figure 4C). These results suggest that the activity of the holoenzyme and not only of the free catalytic subunits, which are known to have functions independent of the regulatory subunits [57], are responsible for the phenotypes observed. Furthermore, the involvement of both Ckb1 and Ckb2 in the regulation of stress resistance is in agreement with the requirement of both regulatory subunits for the full CK2 activation [56].…”

Section: Resultsmentioning

confidence: 81%

“…Lack of Ckb2 promoted a modest but significant (p<0.05) longevity extension and a marked increase of heat resistance in comparison with the wild type (Figure 5B, Figure 6B). Two highly specific CK2 inhibitors, 4,5,6,7-tetrabromo-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-benzimidazole (TBBz), have been identified and shown to inhibit the activity of the holoenzyme [57]. More specifically, in yeast TBBz inhibits the CK2 complex selectively and not the free Cka2 catalytic subunits [57].…”

Section: Resultsmentioning

confidence: 99%

“…Two highly specific CK2 inhibitors, 4,5,6,7-tetrabromo-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-benzimidazole (TBBz), have been identified and shown to inhibit the activity of the holoenzyme [57]. More specifically, in yeast TBBz inhibits the CK2 complex selectively and not the free Cka2 catalytic subunits [57]. We tested both inhibitors in our system and found that TBBz (10–200 µM) but not TBBt (5–15 µM) increased substantially the heat resistance of day 3 DBY746 cultures (Figure 6C, Figure S3A).…”

Section: Resultsmentioning

confidence: 99%

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Genome-Wide Screen in Saccharomyces cerevisiae Identifies Vacuolar Protein Sorting, Autophagy, Biosynthetic, and tRNA Methylation Genes Involved in Life Span Regulation

et al. 2010

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The study of the chronological life span of Saccharomyces cerevisiae, which measures the survival of populations of non-dividing yeast, has resulted in the identification of homologous genes and pathways that promote aging in organisms ranging from yeast to mammals. Using a competitive genome-wide approach, we performed a screen of a complete set of approximately 4,800 viable deletion mutants to identify genes that either increase or decrease chronological life span. Half of the putative short-/long-lived mutants retested from the primary screen were confirmed, demonstrating the utility of our approach. Deletion of genes involved in vacuolar protein sorting, autophagy, and mitochondrial function shortened life span, confirming that respiration and degradation processes are essential for long-term survival. Among the genes whose deletion significantly extended life span are ACB1, CKA2, and TRM9, implicated in fatty acid transport and biosynthesis, cell signaling, and tRNA methylation, respectively. Deletion of these genes conferred heat-shock resistance, supporting the link between life span extension and cellular protection observed in several model organisms. The high degree of conservation of these novel yeast longevity determinants in other species raises the possibility that their role in senescence might be conserved.

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Genome-Wide Screen in Saccharomyces cerevisiae Identifies Vacuolar Protein Sorting, Autophagy, Biosynthetic, and tRNA Methylation Genes Involved in Life Span Regulation

et al. 2010

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“…TBBz has been shown to inhibit specifically the CkII holoenzyme by ATP competition with effective concentrations in yeast of 10-200 µm (Fabrizio et al, 2010; Zień et al, 2003). We observed that pharmacological inhibition of CkII, using 200 µm TBBz, in flies overexpressing slgA-D or -E in the LNv, leads to hyperaggression compared with control flies (Fig.…”

Section: Resultsmentioning

confidence: 99%

SlgA, the homologue of the human schizophrenia associated PRODH gene, acts in clock neurons to regulate Drosophila aggression

Zwarts

Vulsteke

Buhl

et al. 2017

Disease Models &Amp; Mechanisms

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Mutations in the proline dehydrogenase gene PRODH are linked to behavioral alterations in schizophrenia and as part of DiGeorge and velo-cardio-facial syndromes, but the role of PRODH in their etiology remains unclear. Here, we establish a Drosophila model to study the role of PRODH in behavioral disorders. We determine the distribution of the Drosophila PRODH homolog slgA in the brain and show that knockdown and overexpression of human PRODH and slgA in the lateral neurons ventral (LNv) lead to altered aggressive behavior. SlgA acts in an isoform-specific manner and is regulated by casein kinase II (CkII). Our data suggest that these effects are, at least partially, due to effects on mitochondrial function. We thus show that precise regulation of proline metabolism is essential to drive normal behavior and we identify Drosophila aggression as a model behavior relevant for the study of the mechanisms that are impaired in neuropsychiatric disorders.

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“…To this end, we investigated the effects of CK2 inhibitors on p53 and HIF-1␣ protein level and activity. Apigenin (Ford et Zhu et al, 2002), DRB (5,6-Dichloro-1-␤-Dribofuranosyl-benzimidazole) (Blaydes and Hupp, 1998;Critchfield et al, 1997;Farah et al, 2003) and TBB (3,4,5,6-tetrabromo-triazole) (Ruzzene et al, 2002;Zien et al, 2003) were used as CK2-specific inhibitors. An inverse relationship was observed with decreased HIF-1 activity in parallel with increased p53 protein level and activity in the presence of these inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level

Hubert

Paris

Piret

et al. 2006

Journal of Cell Science

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HIF-1 (hypoxia-inducible factor-1) is the main transcription factor involved in the adaptation of cells to hypoxia. In addition to regulation of HIF-1α protein level, HIF-1 activity is also enhanced by several pathways involving asparagine hydroxylation and phosphorylation. Here, we investigated the relationship between casein kinase 2 (CK2), p53 and HIF-1. An increase in p53 protein level and transcriptional activity was observed when CK2 was inhibited by different inhibitors under normoxia and hypoxia. This increase was in parallel with a decrease in HIF-1 activity without changes in HIF-1α protein level, indicating a regulation of its transcriptional activity. Similar results were obtained using CK2α siRNA. Ectopic overexpression of p53 also led to an inhibition of HIF-1 activity. Conversely, CK2 inhibition had no effect in p53-null cells indicating that the inhibitory effect of CK2 inhibitors requires the presence of p53. p53 activity was not required because overexpression of a p53 mutated in its DNA-binding domain exerted the same effect as wild-type p53 and because the effect of CK2 inhibitors was still observed when p53 activity was inhibited by pifithrin-α. Since CK2 activity is increased in hypoxic conditions, this process provides one more mechanism to ensure enhanced HIF-1 activity under such conditions.

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TBBz but not TBBt discriminates between two molecular forms of CK2 in vivo and its implications

Cited by 16 publications

References 32 publications

Genome-Wide Screen in Saccharomyces cerevisiae Identifies Vacuolar Protein Sorting, Autophagy, Biosynthetic, and tRNA Methylation Genes Involved in Life Span Regulation

Genome-Wide Screen in Saccharomyces cerevisiae Identifies Vacuolar Protein Sorting, Autophagy, Biosynthetic, and tRNA Methylation Genes Involved in Life Span Regulation

SlgA, the homologue of the human schizophrenia associated PRODH gene, acts in clock neurons to regulate Drosophila aggression

Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level

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