CK2-mediated stimulation of Pol I transcription by stabilization of UBF–SL1 interaction

Lin, Chih-Yin; Navarro, Sonia; Reddy, Sita; Comai, Lucio

doi:10.1093/nar/gkl581

Cited by 42 publications

(43 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CK2 resides in the nucleolus, as well as in the nucleus and cytoplasm, regulates a large number of nucleolar proteins (25) and plays a major role in nucleolar compartmentalization (26). CK2 also regulates the transcriptional activities of all three RNA polymerases (25,(27)(28)(29). In the case of Pol I, CK2 has been found in the rRNA promoter region by ChIP assay and coimmunoprecipitates with the Pol I transcription initiation complex (30,31).…”

Section: Discussionmentioning

confidence: 99%

Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF-IA

Nguyen

Mitchell

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Ribosomal proteins are synthesized in the nucleolus under the control of a number of repetitive DNA elements and are required for cell proliferation. Cancer cells frequently contain mutations that activate the phosphoinositide 3-kinase/Akt signaling pathway. This study shows that activation of Akt enhances the transcription of ribosomal genes by stabilizing a protein, transcription initiation factor I (TIF-IA), which is essential for the transcription of ribosomal DNA. Activated Akt also increases ribosomal RNA synthesis by phosphorylating casein kinase 2, which in turn phosphorylates and enhances the activity of TIF-IA. These results demonstrate new mechanisms by which the activation of Akt can promote tumor cell proliferation and further support the targeting of activated Akt as a potential therapy for certain cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF-IA

Nguyen

Mitchell

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Such a regulatory function is possible for IP5K, which binds CK2, UBF and TCOF1 (Fig. 1F); rRNA synthesis is regulated by interactions between UBF and TCOF1 (Valdez et al, 2004), and also by the phosphorylation of UBF and TCOF1 by CK2 (Isaac et al, 2000;Lin et al, 2006). The facilitation of such communication pathways by IP5K may assist the information flow from cellular signaling cascades, so as to regulate the ribosome production that guides cell differentiation and proliferation (Drygin et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…S3). The actions of both UBF and TCOF1 in vivo are modulated by protein kinase CK2 (CK2) (Isaac et al, 2000;Lin et al, 2006). Indeed, CK2 is a key player in the overall regulation of rRNA synthesis so that the degree of ribosomal production can dynamically match changes in cell growth and proliferation (Drygin et al, 2010).…”

Section: Binding Partners For Ip5kmentioning

confidence: 99%

A non-catalytic role for inositol 1,3,4,5,6-pentakisphosphate 2-kinase in the synthesis of ribosomal RNA

Brehm

Wundenberg

Williams

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryFundamental to the life and destiny of every cell is the regulation of protein synthesis through ribosome biogenesis, which begins in the nucleolus with the production of ribosomal RNA (rRNA). Nucleolar organization is a highly dynamic and tightly regulated process; the structural factors that direct nucleolar assembly and disassembly are just as important in controlling rRNA synthesis as are the catalytic activities that synthesize rRNA. Here, we report that a signaling enzyme, inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP5K) is also a structural component in the nucleolus. We demonstrate that IP5K has functionally significant interactions with three proteins that regulate rRNA synthesis: protein kinase CK2, TCOF1 and upstream-binding-factor (UBF). Through molecular modeling and mutagenic studies, we identified an Arg-Lys-Lys tripeptide located on the surface of IP5K that mediates its association with UBF. Nucleolar IP5K spatial dynamics were sensitive to experimental procedures (serum starvation or addition of actinomycin D) that inhibited rRNA production. We show that IP5K makes stoichiometrically sensitive contributions to the architecture of the nucleoli in intact cells, thereby influencing the degree of rRNA synthesis. Our study adds significantly to the biological significance of IP5K; previously, it was the kinase activity of this protein that had attracted attention. Our demonstration that IP5K 'moonlights' as a molecular scaffold offers an unexpected new example of how the biological sophistication of higher organisms can arise from gene products acquiring multiple functions, rather than by an increase in gene number.

show abstract

“…Several factors can modulate rRNA synthesis through rDNA transcription, such as the cell growth rate, chromatin structure, rDNA copy number, nutritional status, growth factors and chemical stresses [1][2][3][4][5][6]. Studies in human cells have revealed that selectivity factor 1, which binds to the rDNA gene promoter and promotes recruitment of pol I [7], is regulated by casein kinase 2 (CK2), extracellular signal-regulated kinase and mTOR [8][9][10][11]. CK2 modulates the interaction between selectivity factor 1 and upstream binding factor through upstream binding factor phosphorylation [9,12,13], and rRNA synthesis is promoted by AKT in association with c-Myc and mTORC1 in human cancer-derived cells [14].…”

Section: Introductionmentioning

confidence: 99%

“…Studies in human cells have revealed that selectivity factor 1, which binds to the rDNA gene promoter and promotes recruitment of pol I [7], is regulated by casein kinase 2 (CK2), extracellular signal-regulated kinase and mTOR [8][9][10][11]. CK2 modulates the interaction between selectivity factor 1 and upstream binding factor through upstream binding factor phosphorylation [9,12,13], and rRNA synthesis is promoted by AKT in association with c-Myc and mTORC1 in human cancer-derived cells [14]. Although the regulation of rDNA transcription has been well characterized, the regulation of RPG transcription is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Casein kinase 2 inhibits HomolD‐directed transcription by Rrn7 in Schizosaccharomyces pombe

et al. 2014

View full text Add to dashboard Cite

In Schizosaccharomyces pombe, ribosomal protein gene (RPG) promoters contain a TATA analogue element called the HomolD box. The HomolD‐binding protein Rrn7 forms a complex with the RNA polymerase II machinery. Despite the importance of ribosome biogenesis to cell survival, the mechanisms involved in the regulation of transcription of eukaryotic RPGs are unknown. In this study, we identified Rrn7 as a new substrate of the pleiotropic casein kinase 2 (CK2), which is a regulator of basal transcription. Recombinant Rrn7 from S. pombe, which is often used as a model organism for studying eukaryotic transcription, interacted with CK2 in vitro and in vivo. Furthermore, CK2‐mediated phosphorylation of Rrn7 inhibited its HomolD‐directed transcriptional activity and ability to bind to an oligonucleotide containing a HomolD box in vitro. Mutation of Rrn7 at Thr67 abolished these effects, indicating that this residue is a critical CK2 phosphorylation site. Finally, Rrn7 interacted with the regulatory subunit of CK2 in vivo, inhibition of CK2 in vivo potentiated ribosomal protein gene transcription, and chromatin immunoprecipitation analyses identified that the catalytic subunit of CK2 was associated with the rpk5 gene promoter in S. pombe. Taken together, these data suggest that CK2 inhibits ribosomal protein gene transcription in S. pombe via phosphorylation of Rrn7 at Thr67.

show abstract

CK2-mediated stimulation of Pol I transcription by stabilization of UBF–SL1 interaction

Cited by 42 publications

References 64 publications

Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF-IA

Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF-IA

A non-catalytic role for inositol 1,3,4,5,6-pentakisphosphate 2-kinase in the synthesis of ribosomal RNA

Casein kinase 2 inhibits HomolD‐directed transcription by Rrn7 in Schizosaccharomyces pombe

Contact Info

Product

Resources

About