Flow cytometric analysis of cellular DNA content showed that LKB1 loss did not block cell cycle entry, as LKB1-null pre-T cells can enter the proliferative S/G2 phases of the cell cycle albeit at a reduced frequency compared to controls (Fig. 3B).
Interestingly, blocking cell cycle re-entry with a DNA synthesis inhibitor, prevents adipocyte differentiation, suggesting that an active cell cycle machinery is required for the differentiation process (Richon et al, 1997).
Blockade of the EGFR/ERK pathway prevents G3 induced expression of CDK2 and GSK-3β (S9P) and as a result blocks cell cycle entry.
PTEN-KD significantly attenuated the anti-estrogen effect in blocking cell cycle S-phase entry, which partially explains the cell growth advantage over PTEN-WT cells (Additional file 5: Figure S5A).
Conversely, TGFbeta blocked cell cycle progression, diminished CCC DNA synthesis but increased viral transcription.
Therefore, growth inhibition by BLU may result from the blocking of cell cycle entry.
Intriguingly, the effects of proteasome inhibitors on blocking the cell cycle entry of T cells and reducing the severity of some immune-mediated disorders have been demonstrated [ 47, 50, 51].
Furthermore, 14-3-3σ can link to CDK2 and CDK4 and block the cell cycle entry [ 13].
In addition, HSCs harbouring non-repairable DNA damage, such as dysfunctional telomeres, are depleted by apoptosis upon cell cycle activation or blocked from cell cycle entry by induction of senescence (Wang et al., 2014).
We know this because if progression through the cycle is blocked, cell cycle-related neuronal death (CRND) is also blocked.
