SV40-mediated immortalization of human fibroblasts.
We have identified a multistep mechanism by which the DNA virus SV40 overcomes cellular senescence. Expression of SV40 T antigen is required for both transient extension of life span and unlimited life span or immortalization. These effects are mediated through inactivation of function of growth suppressors pRB and p53 via complex formation with T antigen. However, immortalization additionally requires inactivation of a novel growth suppressor gene, which has recently been identified to be on the distal portion of the long arm of chromosome 6, designated SEN6. We propose that SEN6 is responsible for cellular senescence in fibroblasts and other cells.
Ozer
H L
HL
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark 07103, USA.
Banga
S S
SS
Dasgupta
T
T
Houghton
J
J
Hubbard
K
K
Jha
K K
KK
Kim
S H
SH
Lenahan
M
M
Pang
Z
Z
Pardinas
J R
JR
Patsalis
P C
PC
D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D002472:Cell Transformation, Viral; D016922:Cellular Senescence; D005347:Fibroblasts; D016147:Genes, Tumor Suppressor; D006801:Humans; D013539:Simian virus 40 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D000952:Antigens, Polyomavirus Transforming; D016159:Tumor Suppressor Protein p53