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VRK1

Encyclopedia of Signaling Molecules

  • 115 Accesses

Synonyms

Vaccinia-related kinase 1; Vaccinia virus B1R-related kinase 1; VRK1; VRK-1

Historical Background

VRK proteins were identified as two human EST sequences whose translation products have homology with the kinase domain of the unique vaccinia virus B1 kinase, from where its name is derived. During its evolution and adaptation to its host, the virus incorporated the cellular sequence required for viral life-cycle regulation. VRK1 is a chromatin kinase that regulates multiple processes, reflecting its late appearance in evolution as coordinator of preexisting functions in higher eukaryotes.

VRK1 Gene Structure and Expression

The human VRK1 gene is located on the chromosomal region 14q32.2, contains 12 exons and codes for a protein with 396 amino acids (Nichols and Traktman 2004). This gene has a polymorphism, marker rs722869, which is useful in the identification of population structure and genetic ancestry (Lao et al. 2006). Chromosomal translocations in this region do not...

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References

  • Cantarero L, Sanz-Garcia M, Vinograd-Byk H, Renbaum P, Levy-Lahad E, Lazo PA. VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle. Sci Rep. 2015;5:10543. doi:10.1038/srep10543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cullen CF, Brittle AL, Ito T, Ohkura H. The conserved kinase NHK-1 is essential for mitotic progression and unifying acentrosomal meiotic spindles in Drosophila melanogaster. J Cell Biol. 2005;171:593–602. doi:10.1083/jcb.200706067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi YH, Lim JK, Jeong MW, Kim KT. HnRNP A1 phosphorylated by VRK1 stimulates telomerase and its binding to telomeric DNA sequence. Nucleic Acids Res. 2012;40:8499–518. doi:10.1093/nar/gks634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fedorov O, Marsden B, Pogacic V, Rellos P, Muller S, Bullock AN, et al. A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007;104:20523–8. doi:10.1073/pnas.0708800104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finetti P, Cervera N, Charafe-Jauffret E, Chabannon C, Charpin C, Chaffanet M, et al. Sixteen-kinase gene expression identifies luminal breast cancers with poor prognosis. Cancer Res. 2008;68:767–76.

    Article  CAS  PubMed  Google Scholar 

  • Gonzaga-Jauregui C, Lotze T, Jamal L, Penney S, Campbell IM, Pehlivan D, et al. Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly. JAMA Neurol. 2013;70:1491–8. doi:10.1001/jamaneurol.2013.4598.

    PubMed  PubMed Central  Google Scholar 

  • Guermah M, Palhan VB, Tackett AJ, Chait BT, Roeder RG. Synergistic functions of SII and p300 in productive activator-dependent transcription of chromatin templates. Cell. 2006;125:275–86. doi:10.1016/j.cell.2006.01.055.

    Article  CAS  PubMed  Google Scholar 

  • Hennig EE, Mikula M, Rubel T, Dadlez M, Ostrowski J. Comparative kinome analysis to identify putative colon tumor biomarkers. J Mol Med. 2012;90:447–56. doi:10.1007/s00109-011-0831-6.

    Article  CAS  PubMed  Google Scholar 

  • Kang TH, Kim KT. Negative regulation of ERK activity by VRK3-mediated activation of VHR phosphatase. Nat Cell Biol. 2006;8:863–9.

    Article  CAS  PubMed  Google Scholar 

  • Kang TH, Park DY, Choi YH, Kim KJ, Yoon HS, Kim KT. Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells. Mol Cell Biol. 2007;27:8533–46. doi:10.1128/MCB.00018-07.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang TH, Park DY, Kim W, Kim KT. VRK1 phosphorylates CREB and mediates CCND1 expression. J Cell Sci. 2008;121:3035–41. doi:10.1242/jcs.026757.

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Choi YH, Chang S, Kim KT, Je JH. Defective folliculogenesis in female mice lacking vaccinia-related kinase 1. Sci Rep. 2012a;2:468. doi:10.1038/srep00468.

    PubMed  PubMed Central  Google Scholar 

  • Kim W, Chakraborty G, Kim S, Shin J, Park CH, Jeong MW, et al. Macro histone H2A1.2 (MacroH2A1) protein suppresses mitotic kinase VRK1 during interphase. J Biol Chem. 2012b;287:5278–89. doi:10.1074/jbc.M111.281709.

    Article  CAS  PubMed  Google Scholar 

  • Klerkx EP, Lazo PA, Askjaer P. Emerging biological functions of the vaccinia-related kinase (VRK) family. Histol Histopathol. 2009;24:749–59.

    CAS  PubMed  Google Scholar 

  • Lao O, van Duijn K, Kersbergen P, de Knijff P, Kayser M. Proportioning whole-genome single-nucleotide-polymorphism diversity for the identification of geographic population structure and genetic ancestry. Am J Hum Genet. 2006;78:680–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Borges S, Lazo PA. 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. doi:10.1038/sj.onc.1203709.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Sanchez I, Sanz-Garcia M, Lazo PA. 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. doi:10.1128/MCB.01341-08.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Sanchez I, Valbuena A, Vazquez-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. doi:10.1016/j.febslet.2014.01.040.

    Article  CAS  PubMed  Google Scholar 

  • Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912–34. doi:10.1126/science.1075762.

    Article  CAS  PubMed  Google Scholar 

  • Molitor TP, 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. doi:10.1091/mbc.E13-10-0603.

    Article  PubMed  PubMed Central  Google Scholar 

  • Molitor TP, Traktman P. Molecular genetic analysis of VRK1 in mammary epithelial cells: depletion slows proliferation in vitro and tumor growth and metastasis in vivo. Oncogenesis. 2013;2:e48. doi:10.1038/oncsis.2013.11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monsalve DM, Campillo-Marcos I, Salzano M, Sanz-Garcia M, Cantarero L, Lazo PA. VRK1 phosphorylates and protects NBS1 from ubiquitination and proteasomal degradation in response to DNA damage. BBA Mol Cell Res. 2016;1863:760–9. doi:10.1016/j.bbamcr.2016.02.005.

    CAS  Google Scholar 

  • Moura DS, Fernández IF, Marín-Royo G, López-Sánchez I, Martín-Doncel E, Vega FM, et al. Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation. Sci Rep. 2016;6:28532. doi:10.1038/srep28532.

    Article  PubMed  PubMed Central  Google Scholar 

  • Najmabadi H, Hu H, Garshasbi M, Zemojtel T, Abedini SS, Chen W, et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011;478:57–63. doi:10.1038/nature10423.

    Article  CAS  PubMed  Google Scholar 

  • Nezu J, Oku A, Jones MH, 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.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen TP, Biliciler S, Wiszniewski W, Sheikh K. Expanding phenotype of VRK1 mutations in motor neuron disease. J Clin Neuromuscul Dis. 2015;17:69–71. doi:10.1097/CND.0000000000000096.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nichols RJ, Traktman P. Characterization of three paralogous members of the Mammalian vaccinia related kinase family. J Biol Chem. 2004;279:7934–46.

    Article  CAS  PubMed  Google Scholar 

  • Nichols RJ, Wiebe MS, Traktman P. The vaccinia-related kinases phosphorylate the N′ terminus of BAF, regulating its interaction with DNA and its retention in the nucleus. Mol Biol Cell. 2006;17:2451–64. doi:10.1091/mbc.E05-12-1179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orchard S, Ammari M, Aranda B, Breuza L, Briganti L, Broackes-Carter F, et al. The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases. Nucleic Acids Res. 2014;42:D358–63. doi:10.1093/nar/gkt1115.

    Article  CAS  PubMed  Google Scholar 

  • Park CH, Ryu HG, Kim SH, Lee D, Song H, Kim KT. Presumed pseudokinase VRK3 functions as a BAF kinase. BBA Mol Cell Res. 2015;1853:1738–48. doi:10.1016/j.bbamcr.2015.04.007.

    CAS  Google Scholar 

  • 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. doi:10.1016/j.ajhg.2009.07.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salzano M, Sanz-Garcia M, Monsalve DM, Moura DS, Lazo PA. VRK1 chromatin kinase phosphorylates H2AX and is required for foci formation induced by DNA damage. Epigenetics. 2015;10:373–83. doi:10.1080/15592294.2015.1028708.

    Article  PubMed  PubMed Central  Google Scholar 

  • Salzano M, Vazquez-Cedeira M, Sanz-Garcia M, Valbuena A, Blanco S, Fernandez IF, 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. doi:10.18632/oncotarget.1678.

    Article  PubMed  PubMed Central  Google Scholar 

  • Santos CR, Rodriguez-Pinilla M, Vega FM, Rodriguez-Peralto JL, 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. doi:10.1158/1541-7786.MCR-05-0212.

    Article  CAS  PubMed  Google Scholar 

  • Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. 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. doi:10.1074/mcp.M700586-MCP200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanz-Garcia M, Monsalve DM, Sevilla A, Lazo PA. 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. doi:10.1074/jbc.M112.353102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanz-Garcia M, Vazquez-Cedeira M, Kellerman E, Renbaum P, Levy-Lahad E, Lazo PA. Substrate profiling of human vaccinia-related kinases identifies coilin, a Cajal body nuclear protein, as a phosphorylation target with neurological implications. J Proteome. 2011;75:548–60. doi:10.1016/j.jprot.2011.08.019.

    Article  CAS  Google Scholar 

  • Sevilla A, Santos CR, Barcia R, Vega FM, Lazo PA. c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK). Oncogene. 2004a;23:8950–8. doi:10.1038/sj.onc.1208015.

    Article  CAS  PubMed  Google Scholar 

  • Sevilla A, Santos CR, Vega FM, Lazo PA. 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. 2004b;279:27458–65. doi:10.1074/jbc.M401009200.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1074/jbc.M110.200162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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; doi:10.1212/WNL.0000000000002813.

    PubMed  PubMed Central  Google Scholar 

  • Suzuki Y, Ogawa K, Koyanagi Y. Functional disruption of the moloney murine leukemia virus preintegration complex by vaccinia-related kinases. J Biol Chem. 2010;285:24032–43. doi:10.1074/jbc.M110.116640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valbuena A, Blanco S, Vega FM, Lazo PA. The C/H3 domain of p300 is required to protect VRK1 and VRK2 from their downregulation induced by p53. PLoS One. 2008a;3:e2649. doi:10.1371/journal.pone.0002649.

    Article  PubMed  PubMed Central  Google Scholar 

  • Valbuena A, Castro-Obregon S, Lazo PA. Downregulation of VRK1 by p53 in response to DNA damage is mediated by the autophagic pathway. PLoS One. 2011a;6:e17320. doi:10.1371/journal.pone.0017320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valbuena A, Lopez-Sanchez I, Lazo PA. Human VRK1 is an early response gene and its loss causes a block in cell cycle progression. PLoS One. 2008b;3:e1642. doi:10.1371/journal.pone.0001642.

    Article  PubMed  PubMed Central  Google Scholar 

  • Valbuena A, Lopez-Sanchez I, Vega FM, 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. 2007a;465:219–26. doi:10.1016/j.abb.2007.06.005.

    Article  CAS  PubMed  Google Scholar 

  • Valbuena A, Sanz-Garcia M, Lopez-Sanchez I, Vega FM, Lazo PA. Roles of VRK1 as a new player in the control of biological processes required for cell division. Cell Signal. 2011b;23:1267–72. doi:10.1016/j.cellsig.2011.04.002.

    Article  CAS  PubMed  Google Scholar 

  • Valbuena A, Suarez-Gauthier A, Lopez-Rios F, Lopez-Encuentra A, Blanco S, Fernandez PL, et al. Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas. Lung Cancer. 2007b;58:303–9. doi:10.1016/j.lungcan.2007.06.023.

    Article  PubMed  Google Scholar 

  • Valbuena A, Vega FM, Blanco S, Lazo PA. p53 downregulates its activating vaccinia-related kinase 1, forming a new autoregulatory loop. Mol Cell Biol. 2006;26:4782–93. doi:10.1128/MCB.00069-06.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vazquez-Cedeira M, Barcia-Sanjurjo I, Sanz-Garcia M, Barcia R, Lazo PA. Differential inhibitor sensitivity between human kinases VRK1 and VRK2. PLoS One. 2011;6:e23235. doi:10.1371/journal.pone.0023235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vega FM, Gonzalo P, Gaspar ML, Lazo PA. Expression of the VRK (vaccinia-related kinase) gene family of p53 regulators in murine hematopoietic development. FEBS Lett. 2003;544:176–80.

    Article  CAS  PubMed  Google Scholar 

  • Vega FM, Sevilla A, Lazo PA. p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol Cell Biol. 2004;24:10366–80. doi:10.1128/MCB.24.23.10366-10380.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinograd-Byk H, Sapir T, Cantarero L, Lazo PA, Zeligson S, Lev D, et al. The spinal muscular atrophy with pontocerebellar hypoplasia gene VRK1 regulates neuronal migration through an amyloid-beta precursor protein-dependent mechanism. J Neurosci. 2015;35:936–42. doi:10.1523/JNEUROSCI.1998-14.2015.

    Article  PubMed  Google Scholar 

  • Wiebe MS, Nichols RJ, Molitor TP, Lindgren JK, Traktman P. Mice deficient in the serine/threonine protein kinase VRK1 are infertile due to a progressive loss of spermatogonia. Biol Reprod. 2010;82:182–93. doi:10.1095/biolreprod.109.079095.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Salamanca, E-37007, Spain

    Lara Cantarero, David S. Moura, Marcella Salzano, Diana M. Monsalve, Ignacio Campillo-Marcos, Elena Martín-Doncel & Pedro A. Lazo

  2. Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, E-37007, Spain

    Lara Cantarero, David S. Moura, Marcella Salzano, Ignacio Campillo-Marcos, Elena Martín-Doncel & Pedro A. Lazo

Authors
  1. Lara Cantarero
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  2. David S. Moura
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  3. Marcella Salzano
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  4. Diana M. Monsalve
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  5. Ignacio Campillo-Marcos
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  6. Elena Martín-Doncel
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  7. Pedro A. Lazo
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Correspondence to Lara Cantarero .

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Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

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Cantarero, L. et al. (2016). VRK1. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_561-1

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  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_561-1

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  • Online ISBN: 978-1-4614-6438-9

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Chapter history

  1. Latest

    VRK1
    Published:
    22 February 2017

    DOI: https://doi.org/10.1007/978-1-4614-6438-9_561-2

  2. Original

    VRK1
    Published:
    07 November 2016

    DOI: https://doi.org/10.1007/978-1-4614-6438-9_561-1

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