title: Protein kinase CK2 phosphorylation of EB2 regulates its function in the production of Epstein-Barr virus infectious viral particles.
abstract: The Epstein-Barr Virus (EBV) early protein EB2 (also called BMLF1, Mta, or SM) promotes the nuclear export of a subset of early and late viral mRNAs and is essential for the production of infectious virions. We show here that in vitro, protein kinase CK2alpha and -beta subunits bind both individually and, more efficiently, as a complex to the EB2 N terminus and that the CK2beta regulatory subunit also interacts with the EB2 C terminus. Immunoprecipitated EB2 has CK2 activity that phosphorylates several sites within the 80 N-terminal amino acids of EB2, including Ser-55, -56, and -57, which are localized next to the nuclear export signal. EB2S3E, the phosphorylation-mimicking mutant of EB2 at these three serines, but not the phosphorylation ablation mutant EB2S3A, efficiently rescued the production of infectious EBV particles by HEK293(BMLF1-KO) cells harboring an EB2-defective EBV genome. The defect of EB2S3A in transcomplementing 293(BMLF1-KO) cells was not due to impaired nucleocytoplasmic shuttling of the mutated protein but was associated with a decrease in the cytoplasmic accumulation of several late viral mRNAs. Thus, EB2-mediated production of infectious EBV virions is regulated by CK2 phosphorylation at one or more of the serine residues Ser-55, -56, and -57.
authors: INSERM U758, ENS-Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
authors: Cahora
authors: C
authors: Medina-Palazon
authors: Henri
authors: H
authors: Gruffat
authors: Fabrice
authors: F
authors: Mure
authors: Odile
authors: O
authors: Filhol
authors: Valérie
authors: V
authors: Vingtdeux-Didier
authors: Hervé
authors: H
authors: Drobecq
authors: Claude
authors: C
authors: Cochet
authors: Nicolas
authors: N
authors: Sergeant
authors: Alain
authors: A
authors: Sergeant
authors: Evelyne
authors: E
authors: Manet
mesh_terms: D000595:Amino Acid Sequence; D047390:Casein Kinase II / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators; D014764:Viral Proteins; D012694:Serine; D005982:Glutathione Transferase; D047390:Casein Kinase II
references: Cell. 1991 Jul 26;66(2):383-94
references: 1830244
references: J Biol Chem. 2007 May 25;282(21):15645-51
references: 17363367
references: Virology. 1994 Nov 15;205(1):217-27
references: 7975218
references: J Cell Sci. 1995 Feb;108 ( Pt 2):779-87
references: 7769018
references: J Biol Chem. 1997 Jul 4;272(27):17191-5
references: 9202041
references: J Biol Chem. 1997 Sep 26;272(39):24363-70
references: 9305894
references: Genes Dev. 1998 Mar 15;12(6):868-79
references: 9512520
references: J Virol. 2000 Jul;74(13):6068-76
references: 10846090
references: EMBO J. 2000 Jun 15;19(12):3080-9
references: 10856251
references: J Virol. 2000 Nov;74(21):10142-52
references: 11024143
references: J Virol. 2000 Dec;74(23):11322-8
references: 11070032
references: Mol Cell. 2001 Apr;7(4):899-905
references: 11336712
references: FEBS Lett. 2001 May 4;496(1):44-8
references: 11343704
references: EMBO J. 2001 Oct 15;20(20):5769-78
references: 11598019
references: Nature. 2001 Oct 11;413(6856):644-7
references: 11675789
references: J Biol Chem. 2002 Feb 8;277(6):3935-42
references: 11724776
references: J Virol. 2002 Oct;76(19):9635-44
references: 12208942
references: J Cell Sci. 2002 Oct 15;115(Pt 20):3873-8
references: 12244125
references: J Biol Chem. 2003 Jan 3;278(1):335-42
references: 12403791
references: Oncogene. 2003 Jan 16;22(2):220-32
references: 12527891
references: Mol Cell Biol. 2003 Feb;23(3):975-87
references: 12529402
references: Mol Cell. 2003 Mar;11(3):837-43
references: 12667464
references: Nucleic Acids Res. 2003 Jul 1;31(13):3635-41
references: 12824383
references: J Biol Chem. 2003 Sep 26;278(39):37790-8
references: 12857728
references: Cell. 2004 Apr 30;117(3):311-21
references: 15109492
references: J Biol Chem. 2004 Jul 30;279(31):33001-11
references: 15155762
references: J Virol. 2004 Sep;78(17):9412-22
references: 15308735
references: Nucleic Acids Res. 2004;32(18):5553-69
references: 15486205
references: Nucleic Acids Res. 1983 Mar 11;11(5):1475-89
references: 6828386
references: Virology. 1989 Jan;168(1):101-11
references: 2535897
references: Nucleic Acids Res. 1990 Dec 11;18(23):6835-43
references: 2175879
references: J Virol. 1998 Dec;72(12):9526-34
references: 9811685
references: EMBO J. 1999 Feb 15;18(4):1014-24
references: 10022843
references: J Virol. 1999 Apr;73(4):3246-57
references: 10074178
references: J Virol. 1999 May;73(5):4090-100
references: 10196305
references: Biochem Biophys Res Commun. 1999 Apr 21;257(3):731-7
references: 10208852
references: J Biol Chem. 1999 Oct 8;274(41):28991-8
references: 10506147
references: J Virol. 2005 Apr;79(7):3949-61
references: 15767397
references: Biochem J. 2005 Apr 15;387(Pt 2):295-308
references: 15537388
references: Curr Opin Cell Biol. 2005 Jun;17(3):242-50
references: 15901492
references: J Virol. 2005 Nov;79(22):14102-11
references: 16254345
references: J Biol Chem. 2005 Nov 4;280(44):36935-45
references: 16129689
references: Mol Cell Biol. 2006 Mar;26(5):1631-43
references: 16478985
references: J Biol Chem. 2006 Oct 20;281(42):31188-201
references: 16895915
references: J Biol Chem. 2006 Dec 1;281(48):36915-28
references: 17001072
references: Cell. 2006 Dec 29;127(7):1389-400
references: 17190602
references: J Virol. 2007 Apr;81(8):4058-69
references: 17287267
references: Biochemistry. 1991 Nov 19;30(46):11133-40
references: 1932033