Our recent study showed that SAG/RBX2 E3 ubiquitin ligase regulates apoptosis and vasculogenesis by promoting degradation of NOXA and NF1, and co-operates with Kras to promote lung tumorigenesis by activating NFκB and mTOR pathways via targeted degradation of tumor suppressive substrates including IκB, DEPTOR, p21 and p27. Here we investigated the role of Sag/Rbx2 E3 ligase in cellular senescen...

Research on cell senescence and immortalization of murine embryonic fibroblasts (MEFs) has revealed important clues about genetic control of senescence in humans. To investigate senescence and genetic alterations in the p53 pathway that lead to senescence bypass in culture, we compared the behavior of MEFs from wild-type mice with MEFs from Hupki mice, which harbor a humanized p53 gene. We foun...

The E6 protein of the oncogenic human papillomaviruses (HPVs), in combination with the E7 protein, is essential for the efficient immortalization of human foreskin keratinocytes (HFKs). Since we recently demonstrated that E6 activates the human telomerase reverse transcriptase (hTERT) promoter via a Myc-dependent mechanism, we speculated that overexpressed Myc might be able to substitute for E6...

Dental follicle cells (DFCs) are the precursor cells of periodontium. Under certain differentiation conditions, DFCs can be induced to differentiate into chondrogenic, osteogenic and adipogenic cells. However, DFCs has limited lifespan in vitro, so it's difficult to harvest enough cells for basic research and translational application. pMPH86 is a piggyBac transposon-mediated vector which conta...

The hypothesis that induction of immortalization of rodent cells follows one-hit kinetics was tested by the determination of frequencies of immor talization of Syrian hamster embryo cells after treatment with benzo(a)pyrene, \-rays, or ethylnitrosourea. Contrary to expectation, immortalization did not occur in a single step. Full immortalization appeared to be a process which required at least ...

Previous findings on the induction of immortalization in SHE cells have been explained with the activation/alteration hypothesis which postulates that treatment with a carcinogen results in the induction of a so-called "activated state" which enhances the rate of a probabilistic event in the progeny of the treated cells. This event is supposed to be a mutation. Because it has been recently indi...

Replicative senescence of T cells is correlated with erosion of telomere ends. Telomerase plays a key role in maintaining telomere length. Therefore, it is thought that telomerase regulates the life span of T cells. To test this hypothesis, we have over-expressed human telomerase reverse transcriptase in human CD8(+) T cells. Ectopic expression of human telomerase reverse transcriptase led to i...

The disruption of homeostatic mechanisms that regulate normal cell growth and proliferation is a hallmark of cancer. Experimentally, many of the same genetic changes that lead to abnormal cell proliferation conspire to confer replicative immortality upon cells in culture. Correspondingly, several lines of evidence implicate cellular immortalization as a prerequisite for cell transformation. Rec...

Immortalization of primary cells with telomerase is thought to maintain normal phenotypic properties and avoid chromosomal abnormalities and other cancer-associated changes that occur following simian virus 40 tumor antigen (SV40 Tag) induced immortalization. However, we report that the human telomerase reverse transcriptase (hTERT)-immortalized SWAN-71 trophoblast cell line has a near pentaplo...