Table 1.
Cell cycle regulators role in proliferation.
| Common name | Gene name | Role in cell growth | Effect of inhibition on proliferation |
|---|---|---|---|
| P21/CIP1 | Cyclin-dependent kinase inhibitor 1A (CDKN1A) | The encoded protein binds to and inhibits the activity of cyclin-dependent kinase2 or cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. Its expression is regulated by p53 (21) | Cdkn1a deletion elevates proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (21) |
| p27/Kip1 | Cyclin-dependent kinase inhibitor 1B (CDKN1B) | Controls the progression from G1 to the S phase of the cell cycle in response to both mitogenic and anti-mitogenic stimuli (19). | No information |
| PTEN | Phosphatase and tensin homolog (PTEN) | Controls cell proliferation and survival by regulating cell cycle phases, including the G1/S and G2/M transitions. Involved in genetic transmission during cell cycle, promotes the fidelity of DNA replication and chromosome segregation (19) | PTEN-KO in BMSCs showed an increased proliferation capability but decreased multi-directional differentiation potential (22). |
| P53 | Tumor protein p53 (TP53) | p53 is a transcription factor that protects cells against stress, by modulating genes that induce growth arrest, repair, apoptosis, senescence or altered metabolism (23). | MSCs derived from p53KO mice showed an augmented proliferation rate and a shorter doubling time (24). Spontaneous immortalization of chicken fibroblasts resulted in downregulation of TP53 (15) |
| p15/p16/INK4 | Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) | Those genes encode a cyclin-dependent kinase inhibitor, which forms a complex with CDK4/6, and prevents the activation of the CDK kinases. Thus, the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. | Loss of CDKN2B accelerates SMC proliferation while paradoxically increases vascular apoptosis, due to interaction with the MDM2-p53 pathway (23). CRISPR/Cas9 disruption of p15 in chicken muscle SC increases proliferation capacity (29) |