VRK1 explained
Serine/threonine-protein kinase VRK1 is an enzyme that in humans is encoded by the VRK1 gene.[1] [2]
This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely expressed in human tissues and has increased expression in actively dividing cells, such as those in testis, thymus, fetal liver, and carcinomas. Its protein localizes to the nucleus and has been shown to promote the stability and nuclear accumulation of a transcriptionally active p53 molecule and, in vitro, to phosphorylate Thr18 of p53 and reduce p53 ubiquitination. This gene, therefore, may regulate cell proliferation. This protein also phosphorylates histone, casein, and the transcription factors ATF2 (activating transcription factor 2) and C-jun.[3]
Further reading
- 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. . 44 . 2 . 133–4 . 1999 . 10083742 . 10.1007/s100380050127 . free .
- Sayed M, Kim SO, Salh BS, etal . Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase. . J. Biol. Chem. . 275 . 22 . 16569–73 . 2000 . 10747897 . 10.1074/jbc.M000312200 . free .
- 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 . 19 . 32 . 3656–64 . 2000 . 10951572 . 10.1038/sj.onc.1203709 . free .
- Latonen L, Taya Y, Laiho M . UV-radiation induces dose-dependent regulation of p53 response and modulates p53-HDM2 interaction in human fibroblasts. . Oncogene . 20 . 46 . 6784–93 . 2001 . 11709713 . 10.1038/sj.onc.1204883 . free .
- Barcia R, López-Borges S, Vega FM, Lazo PA . Kinetic properties of p53 phosphorylation by the human vaccinia-related kinase 1. . Arch. Biochem. Biophys. . 399 . 1 . 1–5 . 2002 . 11883897 . 10.1006/abbi.2001.2746 .
- Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
- Nichols RJ, Traktman P . Characterization of three paralogous members of the Mammalian vaccinia related kinase family. . J. Biol. Chem. . 279 . 9 . 7934–46 . 2004 . 14645249 . 10.1074/jbc.M310813200 . free .
- Boyle KA, 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. . 78 . 4 . 1992–2005 . 2004 . 14747564 . 10.1128/JVI.78.4.1992-2005.2004 . 369515 .
- 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. . 279 . 26 . 27458–65 . 2004 . 15105425 . 10.1074/jbc.M401009200 . free .
- Sevilla A, Santos CR, Barcia R, etal . c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK). . Oncogene . 23 . 55 . 8950–8 . 2004 . 15378002 . 10.1038/sj.onc.1208015 . free .
- Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
- Vega FM, Sevilla A, Lazo PA . p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. . Mol. Cell. Biol. . 24 . 23 . 10366–80 . 2005 . 15542844 . 10.1128/MCB.24.23.10366-10380.2004 . 529057 .
- Andersen JS, Lam YW, Leung AK, etal . Nucleolar proteome dynamics. . Nature . 433 . 7021 . 77–83 . 2005 . 15635413 . 10.1038/nature03207 . 2005Natur.433...77A . 4344740 .
- Santos CR, Rodríguez-Pinilla M, Vega FM, etal . VRK1 signaling pathway in the context of the proliferation phenotype in head and neck squamous cell carcinoma. . Mol. Cancer Res. . 4 . 3 . 177–85 . 2006 . 16547155 . 10.1158/1541-7786.MCR-05-0212 . free .
- Valbuena A, Vega FM, Blanco S, Lazo PA . p53 downregulates its activating vaccinia-related kinase 1, forming a new autoregulatory loop. . Mol. Cell. Biol. . 26 . 13 . 4782–93 . 2006 . 16782868 . 10.1128/MCB.00069-06 . 1489172 .
- Valbuena A, López-Sánchez I, Vega FM, etal . Identification of a dominant epitope in human vaccinia-related kinase 1 (VRK1) and detection of different intracellular subpopulations. . Arch. Biochem. Biophys. . 465 . 1 . 219–26 . 2007 . 17617371 . 10.1016/j.abb.2007.06.005 .
Notes and References
- 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 . 45 . 2 . 327–31 . Feb 1998 . 9344656 . 10.1006/geno.1997.4938 .
- Web site: Entrez Gene: VRK1 vaccinia related kinase 1.
- Web site: Entrez Gene: VRK1 vaccinia related kinase 1.