PMID- 16686604
OWN - NLM
STAT- MEDLINE
DCOM- 20060822
LR  - 20211020
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 398
IP  - 1
DP  - 2006 Aug 15
TI  - Differential role played by the MEK/ERK/EGR-1 pathway in orthopoxviruses vaccinia 
      and cowpox biology.
PG  - 83-95
AB  - Appropriation of signalling pathways facilitates poxvirus replication. 
      Poxviruses, as do most viruses, try to modify the host cell environment to 
      achieve favourable replication conditions. In the present study, we show that the 
      early growth response 1 gene (egr-1) is one of the host cell factors intensely 
      modulated by the orthopoxviruses VV (vaccinia virus) and CPV (cowpox virus). 
      These viruses stimulated the generation of both egr-1 mRNA and its gene product, 
      throughout their entire replication cycles, via the requirement of MEK 
      [mitogen-activated protein kinase/ERK (extracellular-signal-regulated kinase) 
      kinase]/ERK pathway. We showed that, upon VV infection, EGR-1 translocates into 
      the nucleus where it binds to the EBS (egr-1-binding site) positioned at the 5' 
      region of EGR-1-regulated genes. In spite of both viruses belonging to the same 
      genus, several lines of evidence, however, revealed a remarkable contrast between 
      them as far as the roles played by the MEK/ERK/EGR-1 pathway in their biological 
      cycles are concerned. Hence (i) the knocking-down of egr-1 by siRNA (small 
      interfering RNA) proved that this transcription factor is of critical relevance 
      for VV biology, since a decrease of about one log cycle in virus yield was 
      verified, along with a small virus plaque phenotype, whereas the gene silencing 
      did not have a detrimental effect on either CPV multiplication or viral plaque 
      size; (ii) while both pharmacological and genetic inhibition of MEK/ERK resulted 
      in a significant decrease in VV yield, both approaches had no impact on CPV 
      multiplication; and (iii) CPV DNA replication was unaffected by pharmacological 
      inhibition of MEK/ERK, but phosphorylation of MEK/ERK was dependent on CPV DNA 
      replication, contrasting with a significant VV DNA inhibition and VV DNA 
      replication-independence to maintain ERK1/2 phosphorylation, observed under the 
      same conditions.
FAU - Silva, Patricia N G
AU  - Silva PN
AD  - Grupo de Transducao de Sinal, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
FAU - Soares, Jamaria A P
AU  - Soares JA
FAU - Brasil, Bruno S A F
AU  - Brasil BS
FAU - Nogueira, Sarah V
AU  - Nogueira SV
FAU - Andrade, Anderson A
AU  - Andrade AA
FAU - de Magalhaes, Jose C
AU  - de Magalhaes JC
FAU - Bonjardim, Marisa B
AU  - Bonjardim MB
FAU - Ferreira, Paulo C P
AU  - Ferreira PC
FAU - Kroon, Erna G
AU  - Kroon EG
FAU - Bruna-Romero, Oscar
AU  - Bruna-Romero O
FAU - Bonjardim, Claudio A
AU  - Bonjardim CA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (DNA, Viral)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
SB  - IM
MH  - Animals
MH  - BALB 3T3 Cells
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Cowpox virus/*physiology
MH  - DNA, Viral/genetics
MH  - Early Growth Response Protein 1/genetics/*metabolism
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Gene Silencing
MH  - Genes, Dominant/genetics
MH  - Genes, Immediate-Early/genetics
MH  - MAP Kinase Kinase 1/*metabolism
MH  - Mice
MH  - Mutation/genetics
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Transport
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Regulatory Sequences, Nucleic Acid/genetics
MH  - *Signal Transduction
MH  - Vaccinia virus/*physiology
MH  - Vero Cells
MH  - Virus Replication/genetics
PMC - PMC1525012
EDAT- 2006/05/12 09:00
MHDA- 2006/08/23 09:00
PMCR- 2007/02/15
CRDT- 2006/05/12 09:00
PHST- 2006/05/12 09:00 [pubmed]
PHST- 2006/08/23 09:00 [medline]
PHST- 2006/05/12 09:00 [entrez]
PHST- 2007/02/15 00:00 [pmc-release]
AID - BJ20060509 [pii]
AID - bj3980083 [pii]
AID - 10.1042/BJ20060509 [doi]
PST - ppublish
SO  - Biochem J. 2006 Aug 15;398(1):83-95. doi: 10.1042/BJ20060509.