Ras- and Raf-dependent activation of c-jun transcriptional activity by the hepatitis B virus transactivator pX.
The mechanisms by which pX, the transactivator of the Hepatitis B Virus (HBV), exerts its effects on transcription of viral and cellular genes have not yet been fully clarified. While previous reports suggested the possibility of a direct interaction of pX, which lacks intrinsic DNA-binding activity, with components of the cellular transcription machinery, more recent investigations support the hypothesis that pX might activate cellular kinases involved in transcriptional regulation and growth control. We analysed the mechanisms of c-Jun transcription factor activation by pX and in particular the role of cellular proteins involved in the transduction of mitogenic signals (namely Ha-Ras and Raf-1). In both HeLa and undifferentiated F9 cells pX was able to increase the activity of exogenous transfected c-Jun but not of c-Jun proteins bearing mutations in the serine residues located in the amino-terminal transcriptional activation domain. We show by use of Ha-Ras and Raf-1 dominant negative mutants that both Ha-Ras and Raf-1 are required for pX-induced activation of c-Jun transcriptional activity. In addition we show that pX is able to cooperate with Raf-1 in c-Jun activation. Our results are consistent with the hypothesis that at least one site of action of pX is peripheral and is located upstream of the Ras genes products.
Natoli
G
G
Istituto di I Clinica Medica, Policlinico Umberto I, Università degli studi di Roma La Sapienza, Italy.
Avantaggiati
M L
ML
Chirillo
P
P
Puri
P L
PL
Ianni
A
A
Balsano
C
C
Levrero
M
M
D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D011905:Genes, ras; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D027384:Oncogene Proteins v-raf; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
D016755:Proto-Oncogene Proteins c-jun; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D015500:Chloramphenicol O-Acetyltransferase; D027384:Oncogene Proteins v-raf; D015689:Oncogene Protein p21(ras)