Another example of a TAA with oncogenic potential is p53. The p53 tumor suppressor protein is a transcription factor with sequence-specific DNA binding activity regulating gene expression related to multiple cellular functions including, but not limited to, cell cycle arrest, cell apoptosis, cell grow...
p53 has been shown to be essential for oncogene-induced senescence [29]. For example, the expression of mutant Rat sarcoma virus (RAS) in mouse embryonic fibroblasts results in permanent G1 cell cycle arrest accompanied by a significant increase in the level of p53 and the expression of many...
Soon afterwards, p53 mutants were found to have gain-of-functions, which explain some oncogenic phenotypes of mutated p53 cDNAs [10]. Therefore, a single amino acid change of p53 could switch it from a tumor suppressor to an oncogene. Similar to these studies in tumor cells, the studies of...
p53 is known as the “guardian of the genome” [1,2]. It has an indispensable role in directing cell fate during cellular stresses, such as hypoxia, oncogene activation, metabolic dilemma, ribosomal stress, and
Furthermore, both the enhancer box sequence (CANNTG) in the p53 promoter and the 3′ terminal untranslated region element were critical in mediating the high-level expression of the reporter. We also provided evidence that cellular myelocytomatosis oncogene was a critical player regulating p53 mRNA...
Furthermore, this feedback regulation is specific to Mdm2; in HeLa cells, where p53 is preferentially degraded by viral E6-dependent ubiquitination, depletion of HAUSP fails to activate p53. This study provides an example of an ubiquitin ligase (Mdm2) that is directly regulated by a ...
14) Mdm2 is a product of a proto-oncogene, amplified or otherwise overexpressed in a significant number of human tumors. Its main claim to fame is that it binds tightly to p53 and renders it inactive. This inactivation is achieved through at least two distinct molecular mechanisms (Figure 1)...
The tumor suppressor p53 is a sequence-specific transcription factor that regulates an extensive network of coding genes, long non-coding RNAs and microRNAs, that establish intricate gene regulatory circuits influencing many cellular responses beyond the prototypical control of cell cycle, apoptosis and ...
Thus, we hypothesized that LOH is a second determinant of mutp53 stabilization and GOF in vivo. To test this, we combined the heterozygous hotspot GOF allele R248Q ('p53Q/+')5,10 with the MMTV-Neu ('Neu') oncogene19 expressing additional wild-type HER2 copies selectively in the mammary...
OPEN Oncogene (2017) 36, 2921–2929 www.nature.com/onc ORIGINAL ARTICLE Genome-wide analysis of p53-regulated transcription in Myc-driven lymphomas C Tonelli1, MJ Morelli2, A Sabò2, A Verrecchia1, L Rotta1, T Capra1, S Bianchi2, S Campaner2 and B Amati1,2 The tumour suppressor p53...