Activation of AP-1 signal transduction pathway by SARS coronavirus nucleocapsid protein.
In March 2003, a novel coronavirus was isolated from patients exhibiting atypical pneumonia and subsequently proven to be the causative agent of the disease now referred to as severe acute respiratory syndrome (SARS). The complete genome of the SARS coronavirus (SARS-CoV) has since been sequenced. The SARS-CoV nucleocapsid (SARS-CoV N) shares little homology with other members of the coronavirus family. To determine if the N protein is involved in the regulation of cellular signal transduction, an ELISA-based assay on transcription factors was used. We found that the amount of transcription factors binding to promoter sequences of c-Fos, ATF2, CREB-1, and FosB was increased by the expression of SARS-CoV N. Since these factors are related to AP-1 signal transduction pathway, we investigated whether the AP-1 pathway was activated by SARS-CoV N protein using the PathDetect system. The results demonstrated that the expression of N protein, not the membrane protein (M), activated AP-1 pathway. We also found that SARS-CoV N protein does not activate NF-kappaB pathway, demonstrating that activation of important cellular pathways by SAS-CoV N protein is selective. Thus our data for the first time indicate that SARS-CoV has encoded a strategy to regulate cellular signaling process.
He
Runtao
R
National Microbiology Laboratory, Health Canada, 1015 Arlington Street, R3E 3R2, Winnipeg, MB, Canada. Runtao_He@hc-sc.gc.ca
Leeson
Andrew
A
Andonov
Anton
A
Li
Yan
Y
Bastien
Nathalie
N
Cao
Jingxin
J
Osiowy
Carla
C
Dobie
Frederick
F
Cutts
Todd
T
Ballantine
Melissa
M
Li
Xuguang
X
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
D019590:Nucleocapsid Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors