PMID- 9499057
OWN - NLM
STAT- MEDLINE
DCOM- 19980312
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 72
IP  - 3
DP  - 1998 Mar
TI  - p53 and RPA are sequestered in viral replication centers in the nuclei of cells 
      infected with human cytomegalovirus.
PG  - 2033-9
AB  - Previously, we reported that human cytomegalovirus (HCMV) infection of 
      fibroblasts markedly affects p53 and other regulatory proteins and inhibits 
      transit through the cell cycle (F. M. Jault, J.-M. Jault, F. Ruchti, E. A. 
      Fortunato, C. Clark, J. Corbeil, D. D. Richman, and D. H. Spector, J. Virol. 
      69:6697-6704, 1995). Although the p53 steady-state levels are elevated throughout 
      the infection, evidence suggests that the ability of p53 to transactivate some of 
      its downstream targets is compromised. To elucidate the mechanisms governing the 
      accumulation of p53, we examined the synthesis, stability, and localization of 
      the protein in HCMV-infected fibroblasts. Synthesis of p53 was not increased in 
      the infected cells during the first 24 h postinfection. In fact, pulse-chase 
      experiments revealed that synthesis of p53 in infected fibroblasts was lower than 
      in mock-infected cells. However, after an initial decay, the p53 was stabilized. 
      In addition, beginning at approximately 30 h postinfection, p53 was localized to 
      discrete foci within the nuclei of infected cells. The morphology of these foci 
      suggested that they were replication centers. We confirmed that these are sites 
      of DNA replication by demonstrating both incorporation of bromodeoxyuridine and 
      localization of UL44 (the viral polymerase processivity factor) into these 
      centers. The single-stranded DNA binding protein RPA was also sequestered. In 
      contrast, Rb and HCMV IE1 72 remained distributed throughout the infected cell 
      nuclei, indicating specific targeting of certain proteins. Taken together, our 
      results provide two alternative mechanisms to account for the increased 
      steady-state levels of p53 observed in HCMV-infected fibroblasts.
FAU - Fortunato, E A
AU  - Fortunato EA
AD  - Department of Biology, University of California, San Diego, La Jolla 92093-0357, 
      USA.
FAU - Spector, D H
AU  - Spector DH
LA  - eng
GR  - R01 CA034729/CA/NCI NIH HHS/United States
GR  - T32 AI007036/AI/NIAID NIH HHS/United States
GR  - CA34729/CA/NCI NIH HHS/United States
GR  - T32AI07036/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ICP36 protein, Cytomegalovirus)
RN  - 0 (IE1 protein, cytomegalovirus)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (RPA1 protein, human)
RN  - 0 (Replication Protein A)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Cytomegalovirus/*metabolism
MH  - *DNA Replication
MH  - DNA-Binding Proteins/analysis/*metabolism
MH  - Fibroblasts/cytology/*metabolism/virology
MH  - Humans
MH  - Immediate-Early Proteins/analysis
MH  - Replication Protein A
MH  - Retinoblastoma Protein/analysis
MH  - Tumor Suppressor Protein p53/biosynthesis/*metabolism
MH  - Viral Proteins/analysis
MH  - *Virus Replication
PMC - PMC109496
EDAT- 1998/03/14 00:00
MHDA- 1998/03/14 00:01
PMCR- 1998/03/01
CRDT- 1998/03/14 00:00
PHST- 1998/03/14 00:00 [pubmed]
PHST- 1998/03/14 00:01 [medline]
PHST- 1998/03/14 00:00 [entrez]
PHST- 1998/03/01 00:00 [pmc-release]
AID - 1684 [pii]
AID - 10.1128/JVI.72.3.2033-2039.1998 [doi]
PST - ppublish
SO  - J Virol. 1998 Mar;72(3):2033-9. doi: 10.1128/JVI.72.3.2033-2039.1998.