Adenovirus type 12 early region 1B 54K protein significantly extends the life span of normal mammalian cells in culture

Abstract

The life span of normal human cells in culture is extended by two to four total life spans following retrovirus-mediated transfer of the adenovirus type 12 E1B 54,000-molecular-weight protein (54K protein). This extension of the in vitro growth potential was accomplished without any of the obvious changes in morphology or growth properties that are usually associated with viral transformation. These 54K+ cells escape the normal senescence checkpoint (M1) and show a very extended secondary growth phase. The 54K+ human cells eventually enter crisis (M2), which does not appear to be due to either telomere attrition or the activation of the senescence-associated proteins p21SdilCipIWaf1 and p16INK4A. Even in the absence of telomerase activity, high-molecular-weight heterogeneous telomeres are produced and maintained in both 54K+ adult dermal fibroblasts and embryo kidney cells, indicating that the 54K protein may interfere with the normal metabolism of telomeric structures during cell division. These findings are discussed with reference to the known ability of the 54K protein to influence p53 function.