vaccinia related kinase 1

Summary

Gene Symbol: vaccinia related kinase 1
Description: vaccinia related kinase 1
Alias: PCH1, PCH1A, serine/threonine-protein kinase VRK1, vaccinia virus B1R-related kinase 1
Species: human
Products:     vaccinia related kinase 1

Top Publications

  1. López Sánchez I, Sanz Garcia M, Lazo P. Plk3 interacts with and specifically phosphorylates VRK1 in Ser342, a downstream target in a pathway that induces Golgi fragmentation. Mol Cell Biol. 2009;29:1189-201 pubmed publisher
    ..The Plk3-VRK1 kinase module might represent two consecutive steps of a signaling cascade that participates in the regulation of Golgi fragmentation. ..
  2. Jeong M, Kang T, Kim W, Choi Y, Kim K. Mitogen-activated protein kinase phosphatase 2 regulates histone H3 phosphorylation via interaction with vaccinia-related kinase 1. Mol Biol Cell. 2013;24:373-84 pubmed publisher
    ..Furthermore, MKP2 specifically regulated the VRK1-mediated histone H3 phosphorylation at M phase. Taken together, these data suggest a novel function of MKP2 as a negative regulator of VRK1-mediated histone H3 phosphorylation. ..
  3. Barcia R, López Borges S, Vega F, Lazo P. Kinetic properties of p53 phosphorylation by the human vaccinia-related kinase 1. Arch Biochem Biophys. 2002;399:1-5 pubmed
    ..The kinase phosphorylates p53 with a K(m) of 1 microM and is well suited to respond to the variations of intracellular p53 concentration, which fluctuates as a response to different types of cellular stress. ..
  4. Sanz Garcia M, Monsalve D, Sevilla A, Lazo P. Vaccinia-related kinase 1 (VRK1) is an upstream nucleosomal kinase required for the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage. J Biol Chem. 2012;287:23757-68 pubmed publisher
    ..VRK1 activation in response to DNA damage is a novel and early step in the signaling of mammalian DNA damage responses. ..
  5. Sevilla A, Santos C, Barcia R, Vega F, Lazo P. c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK). Oncogene. 2004;23:8950-8 pubmed
    ..The VRK1-c-Jun connection represents a component of a new signaling pathway whose upstream elements remain to be identified. ..
  6. Vega F, Sevilla A, Lazo P. p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol Cell Biol. 2004;24:10366-80 pubmed
    ..VRK1 might function as a switch controlling the proteins that interact with p53 and thus modifying its stability and activity. We propose VRK1 as the first step in a new pathway regulating p53 activity during cell proliferation. ..
  7. Santos C, Rodriguez Pinilla M, Vega F, Rodriguez Peralto J, Blanco S, Sevilla A, et al. VRK1 signaling pathway in the context of the proliferation phenotype in head and neck squamous cell carcinoma. Mol Cancer Res. 2006;4:177-85 pubmed
    ..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 G1-S phase. ..
  8. Valbuena A, Vega F, Blanco S, Lazo P. p53 downregulates its activating vaccinia-related kinase 1, forming a new autoregulatory loop. Mol Cell Biol. 2006;26:4782-93 pubmed
    ..The degradation of VRK1 is sensitive to chloroquine, an inhibitor of the late endosome-lysosome transport, and to serine protease inhibitors of the lysosomal pathway. ..
  9. Kang T, Park D, Choi Y, Kim K, Yoon H, Kim K. Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells. Mol Cell Biol. 2007;27:8533-46 pubmed
    ..Overexpression of VRK1 resulted in a dramatic condensation of nuclei. Our findings collectively support a role of VRK1 as a novel mitotic histone H3 kinase in mammals. ..

More Information

Publications75

  1. Valbuena A, Castro Obregón S, Lazo P. Downregulation of VRK1 by p53 in response to DNA damage is mediated by the autophagic pathway. PLoS ONE. 2011;6:e17320 pubmed publisher
    ..This VRK1 downregulation is necessary to modulate the block in cell cycle progression induced by p53 as part of its DNA damage response. ..
  2. Kang T, Park D, Kim W, Kim K. VRK1 phosphorylates CREB and mediates CCND1 expression. J Cell Sci. 2008;121:3035-41 pubmed publisher
    ..Finally, we show that VRK1 is a critical link in the CCND1 gene expression pathway stimulated by Myc overexpression. Our results indicate that VRK1 is a novel regulator of CCND1 expression. ..
  3. Sanz Garcia M, López Sánchez I, Lazo P. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008;7:2199-214 pubmed publisher
  4. Valbuena A, Blanco S, Vega F, Lazo P. The C/H3 domain of p300 is required to protect VRK1 and VRK2 from their downregulation induced by p53. PLoS ONE. 2008;3:e2649 pubmed publisher
    ..These observations point to the relevance of knowing the cofactor levels in order to determine one effect or another. ..
  5. Valbuena A, López Sánchez I, Lazo P. Human VRK1 is an early response gene and its loss causes a block in cell cycle progression. PLoS ONE. 2008;3:e1642 pubmed publisher
    ..VRK1 is an immediate early response gene required for entry in G1, and due to its implication in normal cell proliferation and division, might be a new target for development of inhibitors of cellular proliferation. ..
  6. Kim W, Chakraborty G, Kim S, Shin J, Park C, Jeong M, et al. Macro histone H2A1.2 (macroH2A1) protein suppresses mitotic kinase VRK1 during interphase. J Biol Chem. 2012;287:5278-89 pubmed publisher
    ..2 by NMR spectroscopy. Hence, our findings might provide valuable insight into the underlying molecular mechanism regarding an epigenetic regulation of histone H3 during the cell cycle. ..
  7. Valbuena A, Suarez Gauthier A, Lopez Rios F, Lopez Encuentra A, Blanco S, Fernandez P, et al. Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas. Lung Cancer. 2007;58:303-9 pubmed
    ..The accumulation of VRK1 in tumours with mutant p53 could result in stimulation of other signalling pathways that can contribute to tumour growth and progression in addition to those resulting from loss of p53 function. ..
  8. Valbuena A, López Sánchez I, Vega F, Sevilla A, Sanz Garcia M, Blanco S, et al. Identification of a dominant epitope in human vaccinia-related kinase 1 (VRK1) and detection of different intracellular subpopulations. Arch Biochem Biophys. 2007;465:219-26 pubmed
    ..The different reactivity of the VRK1 protein indicates that this protein has a subcellular localization that can be regulated, thus adding an additional level of regulatory complexity to the VRK1 protein. ..
  9. Sevilla A, Santos C, Vega F, Lazo P. Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK. J Biol Chem. 2004;279:27458-65 pubmed
    ..VRK1 is an element of a novel signaling pathway that regulates gene transcription. ..
  10. Nichols R, Traktman P. Characterization of three paralogous members of the Mammalian vaccinia related kinase family. J Biol Chem. 2004;279:7934-46 pubmed
    ..Our findings provide the basis for further studies of the structure and function of this newly discovered family of protein kinases. ..
  11. Lopez Borges S, Lazo P. The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumour suppressor protein. Oncogene. 2000;19:3656-64 pubmed
    ..We conclude that VRK1 is an upstream regulator of p53 that belongs to a new signalling pathway. ..
  12. Nezu J, Oku A, Jones M, Shimane M. Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to vaccinia virus B1R kinase. Genomics. 1997;45:327-31 pubmed
    ..B1R kinase is reported to be essential for DNA replication of vaccinia virus. The similarity of VRK1 and VRK2 to B1R indicates that these genes may have similar functions. ..
  13. Shin J, Chakraborty G, Bharatham N, Kang C, Tochio N, Koshiba S, et al. NMR solution structure of human vaccinia-related kinase 1 (VRK1) reveals the C-terminal tail essential for its structural stability and autocatalytic activity. J Biol Chem. 2011;286:22131-8 pubmed publisher
    ..These observations also substantiate the role of the extended C-terminal tail in the biological activity of VRK1. ..
  14. Mon A, Mackinnon A, Traktman P. Overexpression of the VRK1 kinase, which is associated with breast cancer, induces a mesenchymal to epithelial transition in mammary epithelial cells. PLoS ONE. 2018;13:e0203397 pubmed publisher
  15. Li N, Wang L, Sun X, Lu Z, Suo X, Li J, et al. A novel mutation in VRK1 associated with distal spinal muscular atrophy. J Hum Genet. 2019;64:215-219 pubmed publisher
    ..In conclusion, our findings identify a novel nonsense mutation p.W375* in the VRK1 gene in a Chinese family with autosomal recessive dSMA and broaden the genetic spectrum of VRK1-associated dSMA. ..
  16. Lee N, Kim D, Han S, Ryu H, Park S, Kim K, et al. Comparative Interactomes of VRK1 and VRK3 with Their Distinct Roles in the Cell Cycle of Liver Cancer. Mol Cells. 2017;40:621-631 pubmed publisher
    ..Thus, this study not only provides a resource for investigating the unidentified functions of VRK1/VRK3, but also an insight into the regulatory roles of VRK1/VRK3 in biological processes. ..
  17. Riggi N, Knoechel B, Gillespie S, Rheinbay E, Boulay G, Suvà M, et al. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell. 2014;26:668-681 pubmed publisher
    ..Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation. ..
  18. Park C, Ryu H, Kim S, Lee D, Song H, Kim K. Presumed pseudokinase VRK3 functions as a BAF kinase. Biochim Biophys Acta. 2015;1853:1738-48 pubmed publisher
    ..These data suggest that VRK3-mediated phosphorylation of BAF may facilitate DNA replication or gene expression by facilitating the dissociation of nuclear envelope proteins and chromatin during interphase. ..
  19. Baratta M, Schinzel A, Zwang Y, Bandopadhayay P, Bowman Colin C, Kutt J, et al. An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma. Proc Natl Acad Sci U S A. 2015;112:232-7 pubmed publisher
    ..Accordingly, primary human xenografts derived from high-MYCN or c-MYC strains exhibited sensitivity to BRD4 inhibition. These data suggest that BRD4 inhibition represents a new therapeutic approach for MYC-overexpressing HGSOCs. ..
  20. Campillo Marcos I, Lazo P. Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?. Cell Mol Life Sci. 2018;75:2375-2388 pubmed publisher
    ..Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage. ..
  21. Kim S, Lyu H, Kim Y, Jeon Y, Kim W, Kim S, et al. Brazilin Isolated from Caesalpinia sappan suppresses nuclear envelope reassembly by inhibiting barrier-to-autointegration factor phosphorylation. J Pharmacol Exp Ther. 2015;352:175-84 pubmed publisher
    ..We propose that brazilin isolated from C. sappan may be a new anticancer drug candidate that induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF phosphorylation. ..
  22. Stoll M, Teoh H, Lee J, Reddel S, Zhu Y, Buckley M, et al. Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia. Neurology. 2016;87:65-70 pubmed publisher
    ..403G>A; p.G135R and c.583T>G; p.L195V, were identified in a child with motor neuron disease. VRK1 mutations can produce adult-onset SMA and motor neuron disease in children without pontocerebellar hypoplasia. ..
  23. Ivanov I, Atkinson D, Litvinenko I, Angelova L, Andonova S, Mumdjiev H, et al. Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature. Eur J Paediatr Neurol. 2018;22:674-681 pubmed publisher
    Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p...
  24. Vinograd Byk H, Renbaum P, Levy Lahad E. Vrk1 partial Knockdown in Mice Results in Reduced Brain Weight and Mild Motor Dysfunction, and Indicates Neuronal VRK1 Target Pathways. Sci Rep. 2018;8:11265 pubmed publisher
    ..Together, our studies of the partial KO Vrk1 mice reveal that even moderately reduced levels of Vrk1 expression result in minor neurological impairment and indicate new neuronal pathways likely involving VRK1. ..
  25. Dobrzynska A, Askjaer P. Vaccinia-related kinase 1 is required for early uterine development in Caenorhabditis elegans. Dev Biol. 2016;411:246-256 pubmed publisher
    ..Moreover, the anchor cell, a specialized uterine cell, fails to fuse with neighboring cells to form the utse syncytium in vrk-1 mutants, thus providing further insight on the role of VRKs in organogenesis. ..
  26. Moura D, Campillo Marcos I, Vázquez Cedeira M, Lazo P. VRK1 and AURKB form a complex that cross inhibit their kinase activity and the phosphorylation of histone H3 in the progression of mitosis. Cell Mol Life Sci. 2018;75:2591-2611 pubmed publisher
    ..The cross inhibition of the kinases at the end of mitosis might facilitate the formation of daughter cells. A sequential role for VRK1, AURKB, and haspin in the progression of mitosis is proposed. ..
  27. Kim S, Ryu H, Lee J, Shin J, Harikishore A, Jung H, et al. Ursolic acid exerts anti-cancer activity by suppressing vaccinia-related kinase 1-mediated damage repair in lung cancer cells. Sci Rep. 2015;5:14570 pubmed publisher
    ..Taken together, UA can be a good anti-cancer agent for targeted therapy or combination therapy with DNA damaging drugs for lung cancer patients. ..
  28. Olson A, Rico A, Wang Z, Delhon G, Wiebe M. Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2. J Virol. 2017;91: pubmed publisher
    ..As a result, we have discovered that B1 and VRK2 target a common set of substrates vital to productive infection of this large cytoplasmic DNA virus. ..
  29. Aihara H, Nakagawa T, Mizusaki H, Yoneda M, Kato M, Doiguchi M, et al. Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via Upregulation of Cyclin D1. Mol Cell. 2016;64:176-188 pubmed publisher
    ..These results suggest that histone H2A T120 phosphorylation by hVRK1 causes inappropriate gene expression, including upregulated cyclin D1, which promotes oncogenic transformation. ..
  30. Hashiguchi T, Arakawa S, Takahashi S, Gonzalez F, Sueyoshi T, Negishi M. Phosphorylation of Farnesoid X Receptor at Serine 154 Links Ligand Activation With Degradation. Mol Endocrinol. 2016;30:1070-1080 pubmed
    ..Thus, FXR Ser154 phosphorylation is a rheostat for activation and subsequent degradation that controls receptor levels and activity. ..
  31. Makunin A, Rajičić M, Karamysheva T, Romanenko S, Druzhkova A, Blagojevic J, et al. Low-pass single-chromosome sequencing of human small supernumerary marker chromosomes (sSMCs) and Apodemus B chromosomes. Chromosoma. 2018;127:301-311 pubmed publisher
    ..Understanding of the non-essential genome elements content provides important insights into genome evolution in general. ..
  32. Varghese R, Liang Y, Guan T, Franck C, Kelly D, Sheng Z. Survival kinase genes present prognostic significance in glioblastoma. Oncotarget. 2016;7:20140-51 pubmed publisher
    ..Importantly, 17 SKGs together presented a novel GBM prognostic signature. SKGs identified herein are associated with recurrence rate and present prognostic significance in GBM, thereby becoming attractive therapeutic targets. ..
  33. Moura D, Fernández I, Marín Royo G, López Sánchez I, Martín Doncel E, Vega F, et al. Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation. Sci Rep. 2016;6:28532 pubmed publisher
    ..2and mH2A2 inhibit CCND1 and VRK1 expression and also block the activation of the VRK1 promoter by Sox2. VRK1 is a downstream target of Sox2 and both form an autoregulatory loop in epithelial cell differentiation. ..
  34. Šmidák R, Mayer R, Bileck A, Gerner C, Mechtcheriakova D, Stork O, et al. Quantitative proteomics reveals protein kinases and phosphatases in the individual phases of contextual fear conditioning in the C57BL/6J mouse. Behav Brain Res. 2016;303:208-17 pubmed publisher
    ..Determination of PKPs in the individual cFC phases represents a valuable resource for interpretation of previous and design of future studies on PKPs in memory mechanisms. ..
  35. Chen K, Zhang S, Ke X, Qi H, Shao J, Shen J. Biphasic reduction of histone H3 phosphorylation in response to N-nitroso compounds induced DNA damage. Biochim Biophys Acta. 2016;1860:1836-44 pubmed publisher
    ..Identification of the dynamic changes and underlying mechanisms of histone modifications upon NOC exposure would be of great help in understanding the epigenetic regulations of NOC induced DNA damage responses. ..
  36. Salzano M, Vázquez Cedeira M, Sanz Garcia M, Valbuena A, Blanco S, Fernández I, et al. Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in human breast cancer by affecting DNA damage response. Oncotarget. 2014;5:1770-8 pubmed
    ..VRK1 is potential target kinase for development of new specific inhibitors which can facilitate sensitization to other treatments in combination therapies; or alternatively be used as a new cancer drugs. ..
  37. Li J, Wang T, Pei L, Jing J, Hu W, Sun T, et al. Expression of VRK1 and the downstream gene BANF1 in esophageal cancer. Biomed Pharmacother. 2017;89:1086-1091 pubmed publisher
    ..790 and 0.735, respectively, for the detection of esophageal squamous cell carcinoma(ESCC) patients. In conclusion, our study indicates that VRK1 and BANF are promising novel therapeutic targets for esophageal cancer. ..
  38. Gotoh S, Miyauchi Y, Moore R, Negishi M. Glucose elicits serine/threonine kinase VRK1 to phosphorylate nuclear pregnane X receptor as a novel hepatic gluconeogenic signal. Cell Signal. 2017;40:200-209 pubmed publisher
    ..Here, serine/threonine kinase, vaccinia related kinase 1 (VRK1)-mediated phosphorylation of PXR is now defined as this glucose-elicited novel signal...
  39. Liu Z, Cao K, Xiao Z, Qiao L, Wang X, Shang B, et al. VRK1 promotes cisplatin resistance by up-regulating c-MYC via c-Jun activation and serves as a therapeutic target in esophageal squamous cell carcinoma. Oncotarget. 2017;8:65642-65658 pubmed publisher
    ..Our studies provide novel insight into the role of VRK1 in carcinogenesis and indicate that VRK1 can serve as a potential therapeutic target in ESCC...
  40. Sugimoto J, Yamauchi T, Hatakeyama T, Isobe M. Isolation and mapping of a polymorphic CA repeat sequence at the human VRK1 locus. J Hum Genet. 1999;44:133-4 pubmed
    ..We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human VRK1 gene. This polymorphism will be useful in genetic studies of disorders localized at the 14q32 region, such as CMIC. ..
  41. Ye Z, Vasco D, Carter T, Brilliant M, Schrodi S, Shukla S. Genome wide association study of SNP-, gene-, and pathway-based approaches to identify genes influencing susceptibility to Staphylococcus aureus infections. Front Genet. 2014;5:125 pubmed publisher
    ..The observed associations could be relevant given the complexity of S. aureus as a pathogen and its ability to exploit multiple biological pathways to cause infections in humans. ..
  42. Ramsuran V, Kulkarni H, He W, Mlisana K, Wright E, Werner L, et al. Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women. Clin Infect Dis. 2011;52:1248-56 pubmed publisher
    ..The trait of Duffy-null-associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa. ..
  43. López Sánchez I, Valbuena A, Vázquez Cedeira M, Khadake J, Sanz Garcia M, Carrillo Jimenez A, et al. VRK1 interacts with p53 forming a basal complex that is activated by UV-induced DNA damage. FEBS Lett. 2014;588:692-700 pubmed publisher
    ..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. ..
  44. Huang W, Cui X, Chen Y, Shao M, Shao X, Shen Y, et al. High VRK1 expression contributes to cell proliferation and survival in hepatocellular carcinoma. Pathol Res Pract. 2016;212:171-8 pubmed publisher
    ..On the basis of these findings, we conclude that VRK1 may be a candidate prognostic biomarker as well as a potential therapeutical target of HCC. ..
  45. Fu T, Ren H, Zhang J, Ren P, Enyedy I, Li G. Role of bivalent cations in structural stabilities of new drug targets--vaccinia-related kinases (VRK) from molecular dynamics simulations. Curr Pharm Des. 2013;19:2269-81 pubmed
  46. Sayed M, Kim S, Salh B, Issinger O, Pelech S. Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase. J Biol Chem. 2000;275:16569-73 pubmed
  47. Latonen L, Taya Y, Laiho M. UV-radiation induces dose-dependent regulation of p53 response and modulates p53-HDM2 interaction in human fibroblasts. Oncogene. 2001;20:6784-93 pubmed
    ..The results suggest that regulation of p53 and HDM2 by UV-radiation is highly dose-dependent and contributes to the outcome of the cellular response. ..
  48. Boyle K, Traktman P. Members of a novel family of mammalian protein kinases complement the DNA-negative phenotype of a vaccinia virus ts mutant defective in the B1 kinase. J Virol. 2004;78:1992-2005 pubmed
  49. Pan B, Lin L, Jiang H, Cai Z, Yu D, Zhuang H. [vrk1 gene mutation test in two Chinese pedigrees of the first and second branchial arch syndrome]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2007;21:1026-8 pubmed
    ..We found a new SNP in proband of Shandong pedigree. vrk1 gene mutation can be excluded in 2 Chinese pedigrees of the first and second branchial arch syndrome. ..
  50. Yan N, Xu H, Zhang J, Xu L, Zhang Y, Zhang L, et al. Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells. Oncotarget. 2017;8:95704-95718 pubmed publisher
    ..In addition, these findings lay foundation to explore the functions of circRNAs in CSCs and indicate that circVRK1 might be a promising target for BCSCs...
  51. Quiel A, Jürgen B, Greinacher A, Lassen S, Wörl R, Witt S, et al. Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical protein chip. Biosens Bioelectron. 2012;36:207-11 pubmed publisher
    ..With this electrical chip assay it is possible to detect antibodies against HPA-1a, HPA-5b and HLA with high sensitivity and specificity in less than half the duration of the MAIPA protocol with similar intra- and interassay variance. ..
  52. Couñago R, Allerston C, Savitsky P, Azevedo H, Godoi P, Wells C, et al. Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations. Sci Rep. 2017;7:7501 pubmed publisher
    ..Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2. ..
  53. Gonzaga Jauregui C, Lotze T, Jamal L, Penney S, Campbell I, Pehlivan D, et al. Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly. JAMA Neurol. 2013;70:1491-8 pubmed publisher
    ..The application of unbiased genomic approaches allows the identification of potentially pathogenic mutations in unsuspected genes in highly genetically heterogeneous and uncharacterized neurological diseases. ..
  54. Cox A, Hugenschmidt C, Raffield L, Langefeld C, Freedman B, Williamson J, et al. Heritability and genetic association analysis of cognition in the Diabetes Heart Study. Neurobiol Aging. 2014;35:1958.e3-1958.e12 pubmed publisher
  55. Liu J, Wang Y, He S, Xu X, Huang Y, Tang J, et al. Expression of vaccinia-related kinase 1 (VRK1) accelerates cell proliferation but overcomes cell adhesion mediated drug resistance (CAM-DR) in multiple myeloma. Hematology. 2016;21:603-612 pubmed
    ..Our data supports a role for VRK1 in MM cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in MM. ..
  56. Salzano M, Sanz García M, Monsalve D, Moura D, Lazo P. VRK1 chromatin kinase phosphorylates H2AX and is required for foci formation induced by DNA damage. Epigenetics. 2015;10:373-83 pubmed publisher
    ..In conclusion, we found that VRK1 is a novel chromatin component that reacts to its alterations and participates very early in DDR, functioning by itself or in cooperation with ATM. ..
  57. Cantarero L, Sanz García M, Vinograd Byk H, Renbaum P, Levy Lahad E, Lazo P. VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle. Sci Rep. 2015;5:10543 pubmed publisher
    ..We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics. ..
  58. Lee N, Kwon J, Kim Y, Kim S, Park S, Xu W, et al. Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition. Oncotarget. 2015;6:30130-48 pubmed publisher
  59. Molitor T, Traktman P. Depletion of the protein kinase VRK1 disrupts nuclear envelope morphology and leads to BAF retention on mitotic chromosomes. Mol Biol Cell. 2014;25:891-903 pubmed publisher
  60. del Puerto Nevado L, Marin Arango J, Fernandez Aceñero M, Arroyo Manzano D, Martinez Useros J, Borrero Palacios A, et al. Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study. BMC Cancer. 2016;16:519 pubmed publisher
  61. Sanz Garcia M, Vázquez Cedeira M, Kellerman E, Renbaum P, Levy Lahad E, Lazo P. Substrate profiling of human vaccinia-related kinases identifies coilin, a Cajal body nuclear protein, as a phosphorylation target with neurological implications. J Proteomics. 2011;75:548-60 pubmed publisher
    ..VRK1 (R358X) is less active than VRK1. Altered regulation of coilin might be implicated in several neurological diseases such as ataxias and spinal muscular atrophies. ..
  62. Ben Z, Gong L, Qiu Y. High expression of VRK1 is related to poor prognosis in glioma. Pathol Res Pract. 2018;214:112-118 pubmed publisher
    ..Besides, reduced expression of VRK1 could induce the apoptosis of glioma cells. On the basis of these findings, we suggested that VRK1 might be a promising prognostic biomarker of glioma. ..
  63. Renbaum P, Kellerman E, Jaron R, Geiger D, Segel R, Lee M, et al. Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. Am J Hum Genet. 2009;85:281-9 pubmed publisher
    ..Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH, also known as pontocerebellar hypoplasia type 1 [PCH1]) is one of the rare infantile SMA variants that include additional clinical manifestations, and its genetic basis ..
  64. Vinograd Byk H, Sapir T, Cantarero L, Lazo P, Zeligson S, Lev D, et al. The spinal muscular atrophy with pontocerebellar hypoplasia gene VRK1 regulates neuronal migration through an amyloid-β precursor protein-dependent mechanism. J Neurosci. 2015;35:936-42 pubmed publisher
    ..APP overexpression rescues the phenotype caused by Vrk1 knockdown, suggesting that VRK1 affects neuronal migration through an APP-dependent mechanism. ..
  65. Supekova L, Supek F, Lee J, Chen S, Gray N, Pezacki J, et al. Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. J Biol Chem. 2008;283:29-36 pubmed
    ..This conclusion was further corroborated by demonstration that replicon cells treated with Csk inhibitor contained lower levels of the phosphorylated form of Fyn than control cells. ..
  66. Monsalve D, Campillo Marcos I, Salzano M, Sanz García M, Cantarero L, Lazo P. VRK1 phosphorylates and protects NBS1 from ubiquitination and proteasomal degradation in response to DNA damage. Biochim Biophys Acta. 2016;1863:760-9 pubmed publisher
    ..We conclude that VRK1 regulation of NBS1 contributes to the stability of the repair complex and permits the sequential steps in DDR. ..