E2F proteins are posttranslationally modified concomitantly with a reduction in nuclear binding activity in cells infected with herpes simplex virus 1

被引:24
作者
Advani, SJ
Weichselbaum, RR
Roizman, B
机构
[1] Univ Chicago, Marjorie B Kovler Viral Oncol Labs, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA
关键词
D O I
10.1128/JVI.74.17.7842-7850.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The transition from G(1) to S phase in the cell cycle requires sequential activation of cyclin-dependent kinase 4 (cdk4) and cdk2, which phosphorylate the retinoblastoma protein, causing the release of E2F. Free E2F upregulates the transcription of genes involved in S phase and cell cycle progression. Recent studies from this and other laboratories have shown that herpes simplex virus 1 stabilizes cyclin D3 early in infection and that early events in viral replication are sensitive to inhibitors of some cdks, On the other hand cdk2 is not activated. Here we report studies on the status of members of E2F family in cycling HEp-2 and HeLa cells and quiescent serum-starved, contact-inhibited human lung fibroblasts. The results show that (i) at 8 h postinfection or thereafter, E2F-1 and E2F-5 were posttranslationally modified and/or translocated from nucleus to the cytoplasm, (ii) E2F-4 was hyperphophorylated, and (iii) overall, E2F binding to cognate DNA sites was decreased at late times after infection. These results concurrent with those cited above indicate that late in infection activation of S-phase genes is blocked both by posttranslational modification and translocation of members of E2F family to inactive compartments and by the absence of active cdk2. The observation that E2F were also posttranslationally modified in quiescent human lung fibroblasts that were not in S phase at the time of infection suggests that specific viral gene products are responsible for modification of the members of E2F family and raises the possibility that in infected cells, activation of the S phase gene is an early event in viral infection and is then shut off at late times. This is consistent with the timing of stabilization of cyclin D3 and the events blocked by inhibitors of cdks.
引用
收藏
页码:7842 / 7850
页数:9
相关论文
共 43 条
  • [1] The disappearance of cyclins A and B and the increase in activity of the G2/M-phase cellular kinase cdc2 in herpes simplex virus 1-infected cells require expression of the α22/US1.5 and UL13 viral genes
    Advani, SJ
    Brandimarti, R
    Weichselbaum, RR
    Roizman, B
    [J]. JOURNAL OF VIROLOGY, 2000, 74 (01) : 8 - 15
  • [2] Regulation of E2F: a family of transcription factors involved in proliferation control
    Black, AR
    Azizkhan-Clifford, J
    [J]. GENE, 1999, 237 (02) : 281 - 302
  • [3] SV40 LARGE TUMOR-ANTIGEN FORMS A SPECIFIC COMPLEX WITH THE PRODUCT OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE
    DECAPRIO, JA
    LUDLOW, JW
    FIGGE, J
    SHEW, JY
    HUANG, CM
    LEE, WH
    MARSILIO, E
    PAUCHA, E
    LIVINGSTON, DM
    [J]. CELL, 1988, 54 (02) : 275 - 283
  • [4] Distinct roles for E2F proteins in cell growth control and apoptosis
    DeGregori, J
    Leone, G
    Miron, A
    Jakoi, L
    Nevins, JR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) : 7245 - 7250
  • [5] THE HUMAN PAPILLOMA VIRUS-16 E7-ONCOPROTEIN IS ABLE TO BIND TO THE RETINOBLASTOMA GENE-PRODUCT
    DYSON, N
    HOWLEY, PM
    MUNGER, K
    HARLOW, E
    [J]. SCIENCE, 1989, 243 (4893) : 934 - 937
  • [6] Herpes simplex virus type 1 infection imposes a G1/S block in asynchronously growing cells and prevents G1 entry in quiescent cells
    Ehmann, GL
    McLean, TI
    Bachenheimer, SL
    [J]. VIROLOGY, 2000, 267 (02) : 335 - 349
  • [7] CHARACTERIZATION OF HERPES SIMPLEX VIRUS STRAINS DIFFERING IN THEIR EFFECTS ON SOCIAL BEHAVIOUR OF INFECTED CELLS
    EJERCITO, PM
    KIEFF, ED
    ROIZMAN, B
    [J]. JOURNAL OF GENERAL VIROLOGY, 1968, 2 : 357 - &
  • [8] E2F-1 functions in mice to promote apoptosis and suppress proliferation
    Field, SJ
    Tsai, FY
    Kuo, F
    Zubiaga, AM
    Kaelin, WG
    Livingston, DM
    Orkin, SH
    Greenberg, ME
    [J]. CELL, 1996, 85 (04) : 549 - 561
  • [10] THE INTERACTION OF RB WITH E2F COINCIDES WITH AN INHIBITION OF THE TRANSCRIPTIONAL ACTIVITY OF E2F
    HIEBERT, SW
    CHELLAPPAN, SP
    HOROWITZ, JM
    NEVINS, JR
    [J]. GENES & DEVELOPMENT, 1992, 6 (02) : 177 - 185