Stein G H, Beeson M, Gordon L
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347.
Science. 1990 Aug 10;249(4969):666-9. doi: 10.1126/science.2166342.
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.
异核体研究表明，衰老和静止的人二倍体成纤维细胞（HDF）含有一种共同的进入S期的抑制剂。通过将衰老和静止的HDF与含有DNA病毒癌基因（如SV40 T抗原、腺病毒E1A或人乳头瘤病毒E7）的细胞融合，可以诱导DNA合成。衰老和静止的HDF都含有视网膜母细胞瘤蛋白的未磷酸化形式（p110Rb），这是一种假定的增殖抑制剂。血清刺激后，衰老的HDF没有使p110Rb磷酸化，也没有进入S期，而静止的HDF使p110Rb磷酸化并进入S期。这些发现，结合T抗原、E1A和E7与未磷酸化的p110Rb形成复合物并可能使其失活的观察结果，表明未能使p110Rb磷酸化可能是衰老的HDF未能进入S期的直接原因。
