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

Jerry W. Shay; Olivia M. Pereira-Smith; Woodring E. Wright

doi:10.1016/0014-4827(91)90453-2

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

Jerry W. Shay, Olivia M. Pereira-Smith, Woodring E. Wright

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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.

Original language	English (US)
Pages (from-to)	33-39
Number of pages	7
Journal	Experimental Cell Research
Volume	196
Issue number	1
DOIs	https://doi.org/10.1016/0014-4827(91)90453-2
State	Published - Sep 1991

ASJC Scopus subject areas

Cell Biology

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10.1016/0014-4827(91)90453-2

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title = "A role for both RB and p53 in the regulation of human cellular senescence",

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.",

author = "Shay, {Jerry W.} and Pereira-Smith, {Olivia M.} and Wright, {Woodring E.}",

note = "Funding Information: This work was supported by NIH Grants AGO7992 (W.E.W. and J.W.S.), POl-AG07123, AGO5333 (O.M.P-S.), andCA50195 (J.W.S.). We thank the following individuals for generously sharing reagents with us: human papilloma virus constructs, P. Howley; adenovirus constructs, L. Babiss; SV40 mutant Kl, D. Livingston; SV40 mutant dlA2433, C. Cole; v-fos retrovirus, FBJ Gross; MLV, R. Liebovitz; MSVhis plasmid, R. Mulligan; CMVElB plasmid and adenovirus ElB monoclonal antibodies, E. White. We also to thank Barbara Quatronne and Steve Harker for technical assistance.",

year = "1991",

month = sep,

doi = "10.1016/0014-4827(91)90453-2",

language = "English (US)",

volume = "196",

pages = "33--39",

journal = "Experimental Cell Research",

issn = "0014-4827",

publisher = "Academic Press Inc.",

number = "1",

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T1 - A role for both RB and p53 in the regulation of human cellular senescence

AU - Shay, Jerry W.

AU - Pereira-Smith, Olivia M.

AU - Wright, Woodring E.

N1 - Funding Information: This work was supported by NIH Grants AGO7992 (W.E.W. and J.W.S.), POl-AG07123, AGO5333 (O.M.P-S.), andCA50195 (J.W.S.). We thank the following individuals for generously sharing reagents with us: human papilloma virus constructs, P. Howley; adenovirus constructs, L. Babiss; SV40 mutant Kl, D. Livingston; SV40 mutant dlA2433, C. Cole; v-fos retrovirus, FBJ Gross; MLV, R. Liebovitz; MSVhis plasmid, R. Mulligan; CMVElB plasmid and adenovirus ElB monoclonal antibodies, E. White. We also to thank Barbara Quatronne and Steve Harker for technical assistance.

PY - 1991/9

Y1 - 1991/9

N2 - 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.

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

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