Regulation of cell proliferation and survival: Convergence of protein kinases and caspases

Duncan, James S.; Turowec, Jacob P.; Vilk, Greg; Li, Shawn S.‐C.; Gloor, Gregory B.; Litchfield, David W.

doi:10.1016/j.bbapap.2009.11.001

Cited by 85 publications

(71 citation statements)

References 80 publications

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“…We have identified kinases that phosphorylate YY1 in vitro, and we mapped several phosphorylation sites on YY1 in vivo (50,51). We provide evidence here that one of these kinases is casein kinase 2␣ (CK2␣), a serine/threonine protein kinase that phosphorylates and regulates many cellular substrates involved in cell growth, proliferation, differentiation, and tumorigenesis (2,10,16,17,32,37). CK2 is ubiquitously present in all eukaryotic cells, highly conserved from yeast to humans, and is constitutively active in cells.…”

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confidence: 92%

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Phosphorylation of the Transcription Factor YY1 by CK2α Prevents Cleavage by Caspase 7 during Apoptosis

Riman

Rizkallah

Kassardjian

et al. 2012

Molecular and Cellular Biology

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In this report, we describe the phosphorylation of Yin Yang 1 (YY1) in vitro and in vivo by CK2␣ (casein kinase II), a multifunctional serine/threonine protein kinase. YY1 is a ubiquitously expressed multifunctional zinc finger transcription factor implicated in regulation of many cellular and viral genes. The products of these genes are associated with cell growth, the cell cycle, development, and differentiation. Numerous studies have linked YY1 to tumorigenesis and apoptosis. YY1 is a target for cleavage by caspases in vitro and in vivo as well, but very little is known about the mechanisms that regulate its cleavage during apoptosis. Here, we identify serine 118 in the transactivation domain of YY1 as the site of CK2␣ phosphorylation, proximal to a caspase 7 cleavage site. CK2␣ inhibitors, as well as knockdown of CK2␣ by small interfering RNA, reduce S118 phosphorylation in vivo and enhance YY1 cleavage under apoptotic conditions, whereas increased CK2␣ activity by overexpression in vivo elevates S118 phosphorylation. A serine-to-alanine substitution at serine 118 also increases the cleavage of YY1 during apoptosis compared to wild-type YY1. Taken together, we have discovered a regulatory link between YY1 phosphorylation at serine 118 and regulation of its cleavage during programmed cell death.

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confidence: 92%

“…CK2 phosphorylation of these proteins occurs at sites flanking their caspase consensus regions, resulting in their protection from caspase-mediated cleavage and apoptosis (14,17,28,31,36,39,53,59,62,66).…”

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confidence: 99%

Phosphorylation of the Transcription Factor YY1 by CK2α Prevents Cleavage by Caspase 7 during Apoptosis

Riman

Rizkallah

Kassardjian

et al. 2012

Molecular and Cellular Biology

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“…More than 300 proteins that are involved in DNA replication, transcription, translation, and signal transduction are phosphorylated by CK2 (8). CK2 is also involved in the regulation of apoptosis (9,10). CK2-dependent phosphorylation of AKT kinase, which is essential for cell survival, activates cells to resist apoptosis (11,12).…”

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confidence: 99%

Structural and functional insights into the regulation mechanism of CK2 by IP ₆ and the intrinsically disordered protein Nopp140

Lee¹,

Son²,

Jin³

et al. 2013

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

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Protein kinase CK2 is a ubiquitous kinase that can phosphorylate hundreds of cellular proteins and plays important roles in cell growth and development. Deregulation of CK2 is related to a variety of human cancers, and CK2 is regarded as a suppressor of apoptosis; therefore, it is a target of anticancer therapy. Nucleolar phosphoprotein 140 (Nopp140), which is an intrinsically disordered protein, interacts with CK2 and inhibits the latter's catalytic activity in vitro. Interestingly, the catalytic activity of CK2 is recovered in the presence of D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (IP 6 ). IP 6 is widely distributed in animal cells, but the molecular mechanisms that govern its cellular functions in animal cells have not been completely elucidated. In this study, the crystal structure of CK2 in complex with IP 6 showed that the lysine-rich cluster of CK2 plays an important role in binding to IP 6 . The biochemical experiments revealed that a Nopp140 fragment (residues 568-596) and IP 6 competitively bind to the catalytic subunit of CK2 (CK2α), and phospho-Ser574 of Nopp140 significantly enhances its interaction with CK2α. Substitutions of K74E, K76E, and K77E in CK2α significantly reduced the interactions of CK2α with both IP 6 and the Nopp140-derived peptide. Our study gives an insight into the regulation of CK2. In particular, our work suggests that CK2 activity is inhibited by Nopp140 and reactivated by IP 6 by competitive binding at the substrate recognition site of CK2.inositol hexakisphosphate | IDP | phosphorylation P rotein phosphorylation is a major aspect of signaling in cells including cell cycle (1). Casein kinase 2 (CK2) is a ubiquitous protein kinase that is essential for cell growth (2), development, and other essential cellular processes (3-7). More than 300 proteins that are involved in DNA replication, transcription, translation, and signal transduction are phosphorylated by CK2 (8). CK2 is also involved in the regulation of apoptosis (9, 10). CK2-dependent phosphorylation of AKT kinase, which is essential for cell survival, activates cells to resist apoptosis (11,12). In addition, CK2-dependent phosphorylation of β-catenin, which induces cell proliferation by Wnt signaling, increases its stability and ability to resist proteolysis (13). Deregulation of CK2 is strongly related to a variety of human cancers (14-17), and therefore, CK2 is considered a target for anticancer therapy (18).Structural and biochemical studies have revealed the molecular architecture and catalytic mechanism of CK2. CK2 consists of two catalytic subunits (α and α′) and two regulatory subunits (β) which can form α 2 β 2 or αα′β 2 heterotetramers (19). The crystal structure of the CK2 holoenzyme is composed of a central dimer of regulatory subunits with catalytic subunits bound to them (20). The active site and residues that are critical for substrate binding have been identified (21). The structure of CK2α in complex with an ATP-analog inhibitor showed a common ATP binding pocket that consists of the residues Lys68,...

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“…CK2 has been shown to be necessary for progression of cells through the cell cycle (2-4) because of phosphorylation of several cell cycle regulators and mitotic proteins (5)(6)(7). It has also been identified as a suppressor of apoptosis (8)(9)(10)(11). The latter role of CK2 has been attributed to phosphorylation of proteins that are directly involved in apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Time schedule-dependent effect of the CK2 inhibitor TBB on PC-3 human prostate cancer cell viability

Orzechowska

Kozłowska²,

Staroń³

et al. 2011

Oncol Rep

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Abstract. Inhibitors of CK2 kinase inhibit cell proliferation and induce apoptosis in numerous cancer cell lines. Due to these properties, they are considered potentially useful in anticancer therapy. In this study, we show that the exact effect of the specific CK2 inhibitor TBB on PC-3 human prostate cancer cell viability depends on the time schedule of administration: it was not observed when the treatment was directly followed by the viability assay but it appeared when the treatment and the assay were separated by a 24-h incubation without the inhibitor. Such a pattern was maintained when the TBB treatment was combined with either camptothecin or TRAIL. The time schedule-dependence of cell viability was not reflected by a similar dependence of induction of apoptosis. Despite this, the schedule in which a treatment with the CK2 inhibitor precedes that with an anticancer drug seems to be a good choice for a potential therapy against androgen-refractory prostate cancer.

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Regulation of cell proliferation and survival: Convergence of protein kinases and caspases

Cited by 85 publications

References 80 publications

Phosphorylation of the Transcription Factor YY1 by CK2α Prevents Cleavage by Caspase 7 during Apoptosis

Phosphorylation of the Transcription Factor YY1 by CK2α Prevents Cleavage by Caspase 7 during Apoptosis

Structural and functional insights into the regulation mechanism of CK2 by IP ₆ and the intrinsically disordered protein Nopp140

Time schedule-dependent effect of the CK2 inhibitor TBB on PC-3 human prostate cancer cell viability

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Regulation of cell proliferation and survival: Convergence of protein kinases and caspases

Cited by 85 publications

References 80 publications

Phosphorylation of the Transcription Factor YY1 by CK2α Prevents Cleavage by Caspase 7 during Apoptosis

Phosphorylation of the Transcription Factor YY1 by CK2α Prevents Cleavage by Caspase 7 during Apoptosis

Structural and functional insights into the regulation mechanism of CK2 by IP 6 and the intrinsically disordered protein Nopp140

Time schedule-dependent effect of the CK2 inhibitor TBB on PC-3 human prostate cancer cell viability

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Structural and functional insights into the regulation mechanism of CK2 by IP ₆ and the intrinsically disordered protein Nopp140