Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of cells in G1 phase with herpes simplex virus (HSV) prevents their progression into S phase (de Bruyn Kops, A., and Knipe, D. M., 1988, Cell 55, 857-868). We have examined G1-phase events in infected cells to determine whether this effect was the result of inhibition of G1 phase progression or of entry into S phase. We observed that HSV infection decreased pRb phosphorylation and induced a new phosphorylated form of pRb. Furthermore, HSV infection prevented the normal G1 increases in cyclin D1 and D3 protein levels, and blocked the normal G1 appearance of new electrophoretic forms of cdk2 and cdk4. Thus, HSV infection inhibits several events that normally occur in the cell cycle during G1 phase, arguing that the HSV-induced block in the cell cycle occurs in early to mid-G1 phase.
 ...
PMID:Herpes simplex virus infection blocks events in the G1 phase of the cell cycle. 1066 28

HSV infection blocks G1 events in the cell cycle and arrests host cell growth in the G1 phase. To further define the mechanism of the effect and determine the viral gene product(s) responsible, we examined various mutant viruses for their effects on cell cycle regulatory proteins (pRb, cyclin D1, and cdk4) and on cell cycle progression into S phase. Unlike the wild-type virus, the ICP27 mutant virus was defective for blocking the phosphorylation of pRb proteins, and the normal pRb pattern was restored in cells infected with a rescued virus. The virion host shutoff (vhs) function, DNA replication, and late gene functions were not required for the virus-induced effects on pRb protein. BrdU incorporation in synchronized HSV-infected cells showed that ICP27 was required for blocking the cell cycle in the G1 phase. Furthermore, ICP27, ICP4, ICP0, and vhs were required for blocking the induction of the G1 cell cycle regulators cyclin D1 and cdk4 in HSV-infected cells. Both ICP27 and the vhs function contributed to the reduction of cyclin D1 mRNA levels in HSV-infected cells: These results provide evidence that HSV-1 ICP27 protein is essential for viral inhibition of G1-phase functions and that certain other HSV proteins are required for some of the viral effects on the cell cycle. Finally, these results show that HSV-1 ICP27 and vhs act jointly to reduce host mRNA levels in infected cells.
 ...
PMID:Herpes simplex virus gene products required for viral inhibition of expression of G1-phase functions. 1188 96