Murine coronavirus nonstructural protein p28 arrests cell cycle in G0/G1 phase

被引:61
作者
Chen, CJ [1 ]
Sugiyama, K [1 ]
Kubo, H [1 ]
Huang, C [1 ]
Makino, S [1 ]
机构
[1] Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
关键词
D O I
10.1128/JVI.78.19.10410-10419.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Murine coronavirus mouse hepatitis virus (MHV) gene 1 encodes several nonstructural proteins. The functions are unknown for most of these nonstructural proteins, including p28, which is encoded at the 5' end of the MHV genome. Transient expression of cloned p28 in several different cultured cells inhibited cell growth, indicating that p28 expression suppressed cell proliferation. Expressed p28 was exclusively localized in the cytoplasm. Cell cycle analysis by How cytometry demonstrated that p28 expression induced G(0)/G(1) cell cycle arrest. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that p28 expression resulted in an accumulation of hypophosphorylated retinoblastoma protein (pRb), tumor suppressor p53, and cyclin-dependent kinase (Cdk) inhibitor p21(Cip1). Expression of p28 did not alter the amount of p53 transcripts yet increased the amount of p21(Cip1) transcripts, suggesting that p28 expression increased p53 stability and that p21(Cip1) was transcriptionally activated in a p53-dependent manner. Our present data suggest the following model of p28-induced G(0)/G(1) cell cycle arrest. Expressed cytoplasmic p28 induces the stabilization of p53, and accumulated p53 causes transcriptional upregulation of p21(Cip1). The increased amount of p21(Cip1) suppresses cyclin E/Cdk2 activity, resulting in the inhibition of pRb hyperphosphorylation. Accumulation of hypophosphorylated pRb thus prevents cell cycle progression from G(0)/G(1) to S phase.
引用
收藏
页码:10410 / 10419
页数:10
相关论文
共 91 条
  • [1] Adams PD, 1996, MOL CELL BIOL, V16, P6623
  • [2] v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation
    Akagi, T
    Shishido, T
    Murata, K
    Hanafusa, H
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (13) : 7290 - 7295
  • [3] HETEROGENEOUS MORPHOLOGIC FEATURES OF PLAQUES INDUCED BY 5 STRAINS OF HUMAN CYTOMEGALO-VIRUS
    ALBRECHT, T
    WELLER, TH
    [J]. AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 1980, 73 (05) : 648 - 654
  • [4] IDENTIFICATION OF A DOMAIN REQUIRED FOR AUTOPROTEOLYTIC CLEAVAGE OF MURINE CORONAVIRUS GENE-A POLYPROTEIN
    BAKER, SC
    SHIEH, CK
    SOE, LH
    CHANG, MF
    VANNIER, DM
    LAI, MMC
    [J]. JOURNAL OF VIROLOGY, 1989, 63 (09) : 3693 - 3699
  • [5] Activation and activities of the p53 tumour suppressor protein
    Bálint, É
    Vousden, KH
    [J]. BRITISH JOURNAL OF CANCER, 2001, 85 (12) : 1813 - 1823
  • [6] Multiple roles of the tumor suppressor p53
    Bargonetti, J
    Manfredi, JJ
    [J]. CURRENT OPINION IN ONCOLOGY, 2002, 14 (01) : 86 - 91
  • [7] Localization of mouse hepatitis virus open reading frame 1A derived proteins
    Bi, WZ
    Piñón, JD
    Hughes, S
    Bonilla, PJ
    Holmes, KV
    Weiss, SR
    Leibowitz, JL
    [J]. JOURNAL OF NEUROVIROLOGY, 1998, 4 (06) : 594 - 605
  • [8] CHARACTERIZATION OF THE LEADER PAPAIN-LIKE PROTEINASE OF MHV-A59 - IDENTIFICATION OF A NEW IN-VITRO CLEAVAGE SITE
    BONILLA, PJ
    HUGHES, SA
    PINON, JD
    WEISS, SR
    [J]. VIROLOGY, 1995, 209 (02) : 489 - 497
  • [9] MOUSE HEPATITIS-VIRUS STRAIN A59 RNA-POLYMERASE GENE ORF 1A - HETEROGENEITY AMONG MHV STRAINS
    BONILLA, PJ
    GORBALENYA, AE
    WEISS, SR
    [J]. VIROLOGY, 1994, 198 (02) : 736 - 740
  • [10] Characterization of a second cleavage site and demonstration of activity in trans by the papain-like proteinase of the murine coronavirus mouse hepatitis virus strain A59
    Bonilla, PJ
    Hughes, SA
    Weiss, SR
    [J]. JOURNAL OF VIROLOGY, 1997, 71 (02) : 900 - 909