A role for both RB and p53 in the regulation of human cellular senescence

JW Shay, OM Pereira-Smith, WE Wright - Experimental cell research, 1991 - Elsevier
JW Shay, OM Pereira-Smith, WE Wright
Experimental cell research, 1991Elsevier
We present evidence for the possible involvement of both the RB and p53 proteins in the
regulation of cellular senescence. Human fibroblasts immortalized with an inducible SV40 T-
antigen become senescent following the de-induction of T-antigen. Plasmids expressing an
alternative source of intact T-antigen restore proliferation but T-antigen deletion mutants
lacking either the RB or p53 binding domains are unable to do so. Similarly, combinations of
adenovirus E1A+ E1B or human papillomavirus E6+ E7 genes are able to replace T-antigen …
Abstract
We present evidence for the possible involvement of both the RB and p53 proteins in the regulation of cellular senescence. Human fibroblasts immortalized with an inducible SV40 T-antigen become senescent following the de-induction of T-antigen. Plasmids expressing an alternative source of intact T-antigen restore proliferation but T-antigen deletion mutants lacking either the RB or p53 binding domains are unable to do so. Similarly, combinations of adenovirus E1A + E1B or human papillomavirus E6 + E7 genes are able to replace T-antigen functions and permit cell proliferation, whereas the individual genes do not. These results are discussed in terms of a two-stage model for the escape from in vitro cellular senescence.
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