P53 tetraploidy checkpoint. Jul 30, 2011 · Highlights Aneuploidy is a tumorigenic process. Shi and King demonstrate that nondisjunction of chromosomes in mitosis frequently results in tetraploidy through mitotic cleavage failure. Oct 23, 2019 · In some somatic cells, tetraploidy results in a p53-dependent cell cycle checkpoint that prevents further cell division 18, 19. Mar 10, 2015 · Tetraploidy in differentiating epiblast cells triggered p53-dependent cell-cycle arrest and apoptosis, suggesting the activation of a tetraploidy checkpoint during early development. Two recent papers address these issues. Aug 14, 2014 · LATS2 is reported to activate p53 by inhibiting Mdm2 (Aylon et al. Tetraploidy in differentiating epiblast cells triggered p53-dependent cell-cycle arrest and apoptosis, suggesting the activation of a tetraploidy checkpoint during early development. Oct 23, 2023 · A new pre-print study suggests that this “stopwatch” is a result of gradual MDM2 degradation that eventually leads to p53 activation in the following G1 (Fulcher et al. Progression to aneuploidy then occurs in the absence of a p53-dependent checkpoint control that normally acts in G 1 to arrest tetraploid cells. As such, the tetraploidy checkpoint may be a critical activity of p53 in its role of ensuring genomic integrity. However, p53 is considered as the key effector of the G1 tetraploidy checkpoint (for review see [87], [90], [107]) and the induction of apoptosis in tetraploid cells [108]. p53 has also been proposed to participate in a “tetraploidy checkpoint” in G1, able to detect and limit the proliferation of tetraploid cells. demonstrate that p53 null tetraploid . In tumorigenesis, aneuploidy is frequently preceded by tetraploidy. Like p53, its paralog and family member p73 also aids in the battle against proliferation of aneuploid cells. Tetraploid cells senesce, apoptosis or arrest, depending on the cellular context. , 2006), and this phenomenon is confirmed in the context of tetraploidy. Inactive checkpoint, excess/deficit centrosomes or mis-cytokinesis cause tetraploidy. Spindle checkpoint, mitotic proteins and p53/p73 determine efficiency of checkpoint. Inactive checkpoint, excess/deficit centrosomes or mis‐cytokinesis cause tetraploidy. In addition, impairment of centrosome integrity activates a p38-p53-p21 checkpoint akin to the “G1 tetraploidy” checkpoint induced by mitotic slippage (for review (Aylon and Oren 2011)). Aneuploidy and p73 As described above, p53 instigates the G1 tetraploidy checkpoint to prevent cells with a 4N DNA content from re‐entering the cell cycle and proliferating. In the Hippo pathway, LATS2 phosphorylates the transcription coactivator YAP to promote YAP cytoplasmic retention and degradation (Yu and Guan, 2013). Fujiwara et al. It has been suggested that there might be a p53 related tetraploidy checkpoint that could permanently block the proliferation of tetraploid cells [4], [14], [15]. 5. May 1, 2024 · The G1 tetraploidy checkpoint is mediated by p53, pRb and others (for review see [105], [106]). Major issues include how tetraploidy arises and how cells can effectively respond to this state. Thus, we propose that a general checkpoint control acts in G1 to recognize tetraploid cells and induce their arrest and thereby prevents the propagation of errors of late mitosis and the generation of aneuploidy. 2023). Mar 10, 2015 · Here, we demonstrated that downregulation of p53, a tumour suppressor protein, rescued tetraploid development in the mammalian epiblast. Aug 1, 2011 · Aneuploidy is a tumorigenic process. Nov 4, 2011 · It is reported that p53 induced apoptosis of tetraploid cells in cultured cancer cell lines and primary mouse mammary epithelial cells [12], [13]. Jul 15, 2002 · Tetraploidy can arise either through disruption of chromosome segregation during mitosis (15 – 18) or through failure of cytokinesis (19). h9l3nxy1 6m0er gy hlff ubt 6anzkqk ah1jpz 03w wsylu nwalq