An early function of the adenoviral E1B 55 kDa protein is required for the nuclear relocalization of the cellular p53 protein in adenovirus-infected normal human cells.
It is well established that the human subgroup C adenovirus type 5 (Ad5) E1B 55 kDa protein can regulate the activity and concentration of the cellular tumor suppressor, p53. However, the contribution(s) of these functions of the E1B protein to viral reproduction remains unclear. To investigate this issue, we examined properties of p53 in normal human cells infected by E1B mutant viruses that display defective entry into the late phase or viral late mRNA export. The steady-state concentrations of p53 were significantly higher in cells infected by the E1B 55 kDa null mutant Hr6 or three mutants carrying small insertions in the E1B 55 kDa protein coding sequence than in Ad5-infected cells. Nevertheless, none of the mutants induced apoptosis in infected cells. Rather, the localization of p53 to E1B containing nuclear sites observed during infection by Ad5 was prevented by mutations that impair interaction of the E1B protein with p53 and/or with the E4 Orf6 protein. These results indicate that the E1B protein fulfills an early function that correlates efficient entry into the late phase with the localization of E1B and p53 in the nucleus of Ad5-infected normal human cells.
Cardoso
F M
FM
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, México.
Kato
Sayuri E M
SE
Huang
Wenying
W
Flint
S Jane
SJ
Gonzalez
Ramon A
RA
D021581:Active Transport, Cell Nucleus; D000256:Adenoviridae / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000502:physiology*; D017504:Adenovirus E4 Proteins / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D017353:Gene Deletion; D006801:Humans; D016254:Mutagenesis, Insertional; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D017501:Adenovirus E1B Proteins; D017504:Adenovirus E4 Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; C056461:terminal protein, adenovirus