c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK)

Sevilla, Ana; Santos, Cláudio R.; Barcia, Ramiro; Vega, Francisco; Lazo, Pedro A.

doi:10.1038/sj.onc.1208015

Cited by 107 publications

(115 citation statements)

References 36 publications

(29 reference statements)

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“…In addition, mutated p53 can sequester VRK1 from its participation in other transcriptional complexes, such as those between VRK1 and Jun [25], ATF2 [26] or CREB [24] and therefore might affect the expression of genes regulated by these transcription factors.…”

Section: Discussionmentioning

confidence: 99%

“…VRK1, the most abundant Ser-Thr kinase in nuclei [23], is a nucleosomal/chromatin kinase that can form complexes and phosphorylate several transcription factors [24][25][26], histones [18,[27][28][29] and other chromatin proteins [30,31]. Moreover, VRK1 kinase activity can also be regulated by these proteins interactions, including those with histones [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

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VRK1 interacts with p53 forming a basal complex that is activated by UV‐induced DNA damage

et al. 2014

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a b s t r a c t DNA damage immediate cellular response requires the activation of p53 by kinases. We found that p53 forms a basal stable complex with VRK1, a Ser-Thr kinase that responds to UV-induced DNA damage by specifically phosphorylating p53. This interaction takes place through the p53 DNA binding domain, and frequent DNA-contact mutants of p53, such as R273H, R248H or R280K, do not disrupt the complex. UV-induced DNA damage activates VRK1, and is accompanied by phosphorylation of p53 at Thr-18 before it accumulates. We propose that the VRK1-p53 basal complex is an early-warning system for immediate cellular responses to DNA damage. Structured summary of protein interactions:VRK1 physically interacts with p53 by anti bait coimmunoprecipitation (1, 2, 3, 4) VRK1 physically interacts with p53 by pull down (1,2,3)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

VRK1 interacts with p53 forming a basal complex that is activated by UV‐induced DNA damage

et al. 2014

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“…The substrates thus far identified regarding the enzymatic activity of VRK1 are transcription factors (23,24) and include p53 (16,22). Therefore, it was decided to study if a correlation FIGURE 1.…”

Section: Vrk1/p53 Pathway In Head and Neck Tumorsmentioning

confidence: 99%

“…21). VRK1 has a serine/threonine kinase activity and phosphorylates several transcription factors, including human p53 (22), and can also cooperate with the c-Jun NH 2 -terminal kinase pathway by phosphorylation of c-Jun (23) and ATF2 (24). All these proteins phosphorylated by VRK1 have been associated with cellular responses to stress (25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

VRK1 Signaling Pathway in the Context of the Proliferation Phenotype in Head and Neck Squamous Cell Carcinoma

Santos

Rodríguez-Pinilla²,

Vega

et al. 2006

Molecular Cancer Research

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105

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The vaccinia-related kinase (VRK) proteins are a new family with three members in the human kinome. The VRK1 protein phosphorylates several transcription factors and has been postulated to be involved in regulation of cell proliferation. In normal squamous epithelium, VRK1 is expressed in the proliferation area. Because VRK1 can stabilize p53, the expression of the VRK1 protein was analyzed in the context of the p53 pathway and the proliferation phenotype in a series of 73 head and neck squamous cell carcinomas. VRK1 protein level positively correlated with p53 response proteins, particularly hdm2 and p21. The VRK1 protein also correlated positively with several proteins associated with proliferation, such as cyclin-dependent kinase 2 (CDK2), CDK6, cdc2, cyclins B1 and A, topoisomerase II, survivin, and Ki67. The level of VRK1 protein behaves like a proliferation marker in this series of head and neck squamous cell carcinomas. To identify a possible regulatory role for VRK1 and because it regulates gene transcription, the promoters of two genes were studied, CDK2 and SURVIVIN, whose proteins correlated positively with VRK1. VRK1 increases the activity of both the CDK2 and SURVIVIN gene promoters. The expression of VRK1 was analyzed in the context of regulators of the G 1 -S transition. VRK1 protein levels increase in response to E2F1 and are reduced by retinoblastoma and p16. These data suggest that VRK1 might play a role in cell cycle regulation and is likely to represent the beginning of a new control mechanism of cell cycle, particularly late in the G 1 -S phase.

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“…Phosphorylated p53 targets VRK1 to the endosome-lysosome degradation pathway, creating an auto-regulatory loop (5,6). VRK1 can also phosphorylate activating transcription factor 2 and c-Jun by its interaction with JNK (7,8). During cell cycle progression, VRK1 has been shown to phosphorylate barrier-to-autointegration factor (BAF), 2 which is believed to compact DNA (9 -11), and it has also been shown to be involved in promoting the transcription of proliferation-related proteins such as retinoblastoma, cyclin-dependent kinase-2, and survivin (12).…”

mentioning

confidence: 99%

Macro Histone H2A1.2 (MacroH2A1) Protein Suppresses Mitotic Kinase VRK1 during Interphase

Kim

Chakraborty

Kim

et al. 2012

Journal of Biological Chemistry

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Background: VRK1 phosphorylates mitotic histone H3 at Thr-3 and Ser-10, but its negative regulator was not elucidated during interphase. Results: The macrodomain of macroH2A1 interacts with VRK1, and this suppresses enzymatic activity of VRK1 during interphase. Conclusion: Specific binding between VRK1 and macroH2A1 is required to regulate the cell cycle-dependent histone H3 phosphorylation. Significance: Understanding epigenetic regulation of histone H3 during the cell cycle is important in cancer development.

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c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK)

Cited by 107 publications

References 36 publications

VRK1 interacts with p53 forming a basal complex that is activated by UV‐induced DNA damage

VRK1 interacts with p53 forming a basal complex that is activated by UV‐induced DNA damage

VRK1 Signaling Pathway in the Context of the Proliferation Phenotype in Head and Neck Squamous Cell Carcinoma

Macro Histone H2A1.2 (MacroH2A1) Protein Suppresses Mitotic Kinase VRK1 during Interphase

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