Blockade of the EGFR/ERK pathway prevents G3 induced expression of CDK2 and GSK-3β (S9P) and as a result blocks cell cycle entry.
Furthermore, 14-3-3σ can link to CDK2 and CDK4 and block the cell cycle entry [ 13].
Therefore, growth inhibition by BLU may result from the blocking of cell cycle entry.
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).
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].
Higher concentrations of cis-UCA slightly increased the fraction of cells in the G0/G1 phase, potentially indicating a block at the cell cycle entry after synchronization.
In contrast, in the ASV-B mice, the transforming activity of the SV40 large T antigen is largely due to its inactivation of the retinoblastoma proteins, which induces cell cycle entry and blocks the p53 tumor suppressor [ 34].
Preventing cyclin C-mediated cell cycle entry or simultaneous blocking of CDK4 and CDK6, both important during G1 progression (Fig. 1), augmented DNA damage upon hydrogen peroxide exposure [ 83, 95].
In addition, both selective EGFR inhibitor AG 1478 and selective MEK inhibitor PD 98059 can block expression of pERK and CDK2, and prevent versican G3 enhanced cell cycle entry and cell growth.
