Murine coronavirus nonstructural protein p28 arrests cell cycle in G 0/G1 phase

Chun Jen Chen, Kazuo Sugiyama, Hideyuki Kubo, Cheng Huang, Shinji Makino

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 flow cytometry demonstrated that p28 expression induced G 0/G1 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 p21Cip1. 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 p21Cip1 was transcriptionally activated in a p53-dependent manner. Our present data suggest the following model of p28-induced G0/G1 cell cycle arrest. Expressed cytoplasmic p28 induces the stabilization of p53, and accumulated p53 causes transcriptional upregulation of p21Cip1. The increased amount of p21Cip1 suppresses cyclin E/Cdk2 activity, resulting in the inhibition of pRb hyperphosphorylation. Accumulation of hypophosphorylated pRb thus prevents cell cycle progression from G0/G1 to S phase.

Original languageEnglish (US)
Pages (from-to)10410-10419
Number of pages10
JournalJournal of Virology
Volume78
Issue number19
DOIs
StatePublished - Oct 2004

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Murine coronavirus
Murine hepatitis virus
G1 Phase
Cell Cycle Checkpoints
interphase
G1 Phase Cell Cycle Checkpoints
cell cycle
Cell Cycle
cyclin-dependent kinase
Cyclin E
Retinoblastoma Protein
Coronavirus
Proteins
Cyclin-Dependent Kinases
proteins
cyclins
S Phase
cultured cells
flow cytometry
cell growth

ASJC Scopus subject areas

  • Immunology

Cite this

Murine coronavirus nonstructural protein p28 arrests cell cycle in G 0/G1 phase. / Chen, Chun Jen; Sugiyama, Kazuo; Kubo, Hideyuki; Huang, Cheng; Makino, Shinji.

In: Journal of Virology, Vol. 78, No. 19, 10.2004, p. 10410-10419.

Research output: Contribution to journalArticle

Chen, Chun Jen ; Sugiyama, Kazuo ; Kubo, Hideyuki ; Huang, Cheng ; Makino, Shinji. / Murine coronavirus nonstructural protein p28 arrests cell cycle in G 0/G1 phase. In: Journal of Virology. 2004 ; Vol. 78, No. 19. pp. 10410-10419.
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