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Science 10 August 1990:
Vol. 249. no. 4969, pp. 666 - 669
DOI: 10.1126/science.2166342
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Articles

Science, Vol 249, Issue 4969, 666-669
Copyright © 1990 by American Association for the Advancement of Science

articles

Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts

GH Stein, M Beeson, and L Gordon

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347.

Heterokaryon studies suggest that senescent and quiescent human diploid fibroblasts (HDF) contain a common inhibitor of entry into S phase. DNA synthesis can be induced in senescent and quiescent HDF by fusing them with cells containing DNA viral oncogenes such as SV40 T antigen, adenovirus E1A, or human papillomavirus E7. Both senescent and quiescent HDF contained the unphosphorylated form (p110Rb) of the retinoblastoma protein, a putative inhibitor of proliferation. After serum stimulation, senescent HDF did not phosphorylate p110Rb and did not enter S phase, whereas quiescent HDF phosphorylated p110Rb and entered S phase. These findings, combined with the observations that T antigen, E1A, and E7 form complexes with, and presumably inactivate, unphosphorylated p110Rb, suggest that failure to phosphorylate p110Rb may be an immediate cause of failure to enter S phase in senescent HDF.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)