XPO1 inhibition induced cell cycle arrest through p53 activation, but the mechanisms of p53 activation differed among the different types of cancer cells. p53 activation depended on the formation of promyelocytic leukemia (PML) nuclear bodies in gastric cancer and liver cancer cells.
We revealed transcriptional downregulation of important p53 acetyltransferases in both CN-AML and APL, accompanied by increased Mdmx protein expression and inadequate Chk2 protein activation.
This work identifies the TP53 tumor suppressor as a novel target through which NPM1-RARA impacts leukemogenesis, and confirms the importance of impairment of TP53 in establishment of the APL phenotype.
According to our results, the pharmacological inhibition of autophagy and p53 mutants are useful tools to explore resistance to apoptosis in APL and other types of cancer and could be the bases of new therapeutic approaches that improve the efficiency and allow dose reduction of the current treatments.
TP53 mutation frequently occurs in solid cancers but not haematological cancers including acute promyelocytic leukaemia (APL) characterised by t(15;17).
We show here that MOZ is an acetyltransferase of p53 at K120 and K382 and colocalizes with p53 in promyelocytic leukemia (PML) nuclear bodies following cellular stress.
We have investigated the cellular effects of the only EBV nuclear protein expressed in GC, EBNA1, focusing on promyelocytic leukemia (PML) nuclear bodies (NBs), which play important roles in apoptosis, p53 activation, and tumor suppression.
Fluorescence in situ hybridization (FISH) was applied to investigate the DNA copy number changes of hTERT, ERG, CDKN1B (P27), CDKN2A (P16), and TP53 genes in an acute promyelocytic leukemia (APL) cell line (NB4).
Fluorescence microscopy studies showed that E1B-55K alone, in the absence of other viral proteins, causes p53 to colocalize with E1B-55K in promyelocytic leukemia (PML) nuclear bodies, nuclear domains with a high concentration of sumoylated proteins.
The promyelocytic leukemia (PML) can selectively and dynamically recruit a number of proteins including p53 to form a sub-nuclear multiprotein chamber named PML-NBs.
It is thus important to find therapeutic agents that can inhibit colon cancer cells with altered p53 status. beta-Lapachone, a novel topoisomerase inhibitor, has been shown to induce cell death in human promyelocytic leukemia and prostate cancer cells through a p53-independent pathway.
We have previously reported the absence of mutations within exons 5-9 of the p53 gene in a panel of 30 cases of acute promyelocytic leukemia (APL), which represent the M3 FAB type of acute myeloid leukemia (AML).
Recently the gene for the cellular tumour antigen p53, a phosphoprotein found in increased concentration in a variety of human cells, had been mapped to region 17q22 by in situ hybridization techniques and has been shown to translocate to the chromosome carrying the translocation [t(15; 17)] associated with acute promyelocytic leukaemia (APL).
Analysis of variant translocations demonstrates that the 15q+ chromosome contains the conserved junction, suggesting a role for p53 in the pathogenesis of APL.