IhNSCs undergo a gradual proliferative arrest during differentiation [18].
Thus, oncogenic RAS causes stable proliferative arrest rather than transformation in diploid fibroblasts [7].
Cellular senescence is characterized by irreversible proliferative arrest, while cells remain viable and metabolically active.
Cell senescence is defined as proliferative arrest that occurs in normal cells after a limited number of cell division.
PPP1CA activation will take part in this second process, contributing to irreversible proliferative arrest by enforcing pRb dephosphorylation.
Silencing of caspase-8 correlates with disruption of differentiation, and increase in replicative capacity, while expression of the DEDs is sufficient to promote differentiation and proliferative arrest.
To further validate a role of the DEDs in proliferative arrest, we used primary endothelial cell cultures, a known model of replicative senescence (Figure S5B and C).
In line with this, here we have shown that interference with βNAC expression levels in Drosophila or human cell lines leads to proliferative arrest, followed by cell death.
Given that their expression changed before any biochemical evidence of proliferative arrest or apoptosis, these genes might be part of an anti-proliferative signaling program activated by gefitinib.
Interestingly, DED association with microtubule-containing structures can influence cell responses to paclitaxel (14), and thus, DED association with microtubules might influence cell division and/or proliferative arrest.
In primary human fibroblasts, CBX7, CBX8, MEL18 and BMI1 are present at the INK4a locus and shRNA-mediated knockdown of any one of these components results in de-repression of INK4a and proliferative arrest.
