CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastomatumor suppressor protein.
Although CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about the clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins.
The retinoblastomatumor suppressor protein (pRb) is a preeminent tumor suppressor that acts as a cell cycle repressor, specifically as an inhibitor of the G1-S transition of the cell cycle . pRb is a phosphoprotein whose function is repressed by extensive phosphorylation in several key residues, and therefore, pRb's phosphorylation status has become a surrogate for pRb activity.
We previously demonstrated a functional role for the cyclin D1/Cdk4/pRb (retinoblastomatumor suppressor protein) pathway in delayed neuronal death induced by ischemia.
At the molecular level, pitavastatin induced expression of the cyclin dependent kinase (CDK) inhibitor p21 in a cholesterol independent manner, blocked repressive phosphorylation of the Retinoblastomatumor suppressor protein at CDK targeted sites, and reduced expression of E2F target genes required for progression through the G1/S boundary.
We further demonstrated that ABT-263 treatment markedly increased the expression of p21<sup>Waf1/Cip1</sup> and decreased the expression of cyclin D1 and phospho-Rb (retinoblastomatumor suppressor protein) (Ser780) proteins that contributed to the G<sub>1</sub>/G<sub>0</sub>-phase arrest.
The retinoblastomatumor suppressor protein (pRB) mediates both transcriptional repression and chromatin organization, but the independent contributions of these functions have been difficult to study.
The retinoblastomatumour suppressor protein (pRb) classically functions to regulate early cell cycle progression where it acts to enforce a number of checkpoints in response to cellular stress and DNA damage.
The family of E2F transcription factors is the key downstream target of the retinoblastomatumor suppressor protein (pRB), which is frequently inactivated in human cancer.
Individual disruption of exon 7 or the projection in RbN or Rb, as occurs in inherited cancers, partially impairs the ability of Rb/RbN to inhibit DNA replication and block G1-to-S cell cycle transit.
We have demonstrated the expression of a viral oncoprotein, the presence of integrated MCPyV, and a truncated LT gene with a preserved retinoblastomatumour-suppressor protein-binding domain in NSCLCs.
Clinical stratification of glioblastoma based on alterations in retinoblastomatumor suppressor protein (RB1) and association with the proneural subtype.
RB1-inducible coiled-coil 1 (RB1CC1, also known as FIP200) is involved in dephosphorylation and increase of retinoblastomatumor suppressor protein (RB1), but the RB1CC1 molecular mechanism in the dephosphorylation of RB1 is not fully understood.
Galectin-3 knockdown in human prostate cancer PC3 cells led to cell-cycle arrest at G(1) phase, up-regulation of nuclear p21, and hypophosphorylation of the retinoblastomatumor suppressor protein (pRb), with no effect on cyclin D1, cyclin E, cyclin-dependent kinases (CDK2 and CDK4), and p27 protein expression levels.
For both bladder and prostate cancer, we have proposed that E2F3 protein overexpression may cooperate with removal of the E2F inhibitor retinoblastomatumor suppressor protein (pRB) to drive cellular proliferation.
Function of the retinoblastomatumor suppressor protein (pRB) may be compromised at a genetic level by gene loss or mutation or at a post-translational level by hyperphosphorylation.
These attributes are due, at least partly, to mutations that directly or indirectly compromise the function of the retinoblastomatumor suppressor protein (pRB), which is a negative regulator of a family of cell-cycle regulatory transcription factors referred to generically as E2F.
We have studied hypoxia-induced cell cycle arrest in human cells where the retinoblastomatumour suppressor protein (pRb) is either functional (T-47D and T-47DHU-res cells) or abrogated by expression of the HPV18 E7 oncoprotein (NHIK 3025 cells).
Ectopic expression of runx2 induces p27KIP1, thereby inhibiting the activity of S-phase cyclin complexes and leading to the dephosphorylation of the retinoblastomatumor suppressor protein (pRb) and a G1 cell cycle arrest.
We have engineered a human adenovirus, ONYX-411, that selectively replicates in human tumor cells, but not normal cells, depending upon the status of their retinoblastomatumor suppressor protein (pRB) pathway.