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. 2019 Sep 3;129(9):3511–3520. doi: 10.1172/JCI129484

Figure 2. Potential mechanisms underlying the stability of EndoC-βH cell lines and the reversion of their immortalization.

Figure 2

Positive or negative variation in RIP activity is counteracted by its effects on SV40LT expression levels at both an individual and a population level. At the individual cell level, an increase (or decrease) in SV40LT expression decreases (or increases) RIP activity by a mechanism involving the Rb pathway. At the cell population level, decrease in SV40LT expression level in a given cell impairs its viability or proliferation compared with the other cells. The result of these mechanistic and selective forces (red and blue arrows) is to keep RIP activity constant in most cells (narrow bell curve). This maintains stable activity within a putative RIP-regulating module, which in turn ensures long-term phenotypic stability. Persistent subthreshold SV40LT expression, as in experiments aimed to reverse immortalization, triggers cell cycle exit and terminal differentiation. For more details, see main text. Rb, activity of the retinoblastoma protein family; RIP, rat insulin promoter; SV40LT, simian virus 40 large T antigen expression.