Kinetic Properties of p53 Phosphorylation by the Human Vaccinia-Related Kinase 1

Barcia, Ramiro; López-Borges, Susana; Vega, Francisco; Lazo, Pedro A.

doi:10.1006/abbi.2001.2746

Cited by 56 publications

(70 citation statements)

References 32 publications

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“…Endogenous VRK1 protein was immunoprecipitated with monoclonal antibody 1F6 as previously reported [44,45] and the immunoprecipitate was used for an in vitro kinase assay [46] showing either endogenous VRK1 autophosphorylation or phosphorylation of GST-p53 (1-85) used as substrate [7,[46][47][48]. The kinase assay was performed at 30°C for 30 min as previously described [47,48].…”

Section: In Vitro Kinase Assaymentioning

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: In Vitro Kinase Assaymentioning

confidence: 99%

“…The kinase assay was performed at 30°C for 30 min as previously described [47,48]. Samples were fractionated by SDS-PAGE and radioactivity was detected by exposure to X-ray film in the linear response range.…”

Section: In Vitro Kinase Assaymentioning

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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“…VRK1 has an affinity for c-Jun, with a Km of 0.4 mM (Figure 2b), which is well suited for the intracellular concentrations of the c-Jun protein. The strong signal of the GST-VRK1 protein is due to the high autophosphorylation activity of this kinase (LopezBorges and Lazo, 2000;Barcia et al, 2002).…”

Section: Vrk1 Phosphorylates C-jun In Vitro and Is Insensitive To Sp6mentioning

confidence: 99%

“…Also, the substrate characteristics are different from those of casein kinase 1 (Lopez-Borges and Lazo, 2000). VRK1 is a nuclear kinase, detected in both murine and human cells, that regulates p53 by phosphorylation in Thr18 (Lopez-Borges and Lazo, 2000; Barcia et al, 2002). Owing to the relation of p53 to cellular stress responses we decided to determine whether the VRK1 kinase was also able to phosphorylate other proteins, which are known to be involved in response to different types of stress signals.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

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“…VRK1, a new regulator of p53, phosphorylates p53 in Thr 18 (22,45), resulting in its stabilization and favoring its interaction with the transcriptional coactivator p300 (16). Phosphorylated Thr 18 affects the interaction of p53 with hdm2 (46,47), and it is acquiring more relevance lately (48,49), particularly because phosphorylation in other better known residues, such as Ser 15 or Ser 20 , seems to be dispensable for p53 activity (49)(50)(51).…”

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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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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Kinetic Properties of p53 Phosphorylation by the Human Vaccinia-Related Kinase 1

Cited by 56 publications

References 32 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

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

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

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