Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations. Here we demonstrate that a TP53 GOF mutation promotes...
Mutant p53 can attenuate the function of wild-type p53, p63 and p73. An aggregation-nucleating sequence in p53 that is revealed in structurally destabilized mutants can induce coaggregation with p63 and p73, resulting in their sequestration in cellular i
Some of the mutations gain additional oncogenic functions and are known as gain-of-function (GOF) mutations. This study analyzed the association among primary tumor site (PS), genome-wide DNA methylation status (GWMS), and TP53 mutation subtypes about prognosis in metastatic colorectal cancer (mC...
Therefore, it is reasonable to study the critical function of the mutant p53 signaling pathway in cancer. Although p53 mutation is a major drive of cancer, the incurable nature of cancer remains elusive. TP53 has a high mutation rate in colorectal cancer mainly due to the change of hydrogen ...
PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas. ...
Global regions of gain and loss in TP53 mutation-positive HGSC cases.Paulina M. WojnarowiczKathleen Klein OrosMichael C. J. QuinnSuzanna L. ArcandKaren GambaroJason MadoreAshley H. BirchManon de LadurantayeKurosh RahimiDiane M. Provencher
a process of gradual loss of cell or lineage identity and gain of properties of embryonic neural cells. Cancer initiation may be the result of activation/upregulation/gain of function of just a single or a few neural genes/proteins, e.g. KRAS, CTNNB1, MYC, EZH2, etc. At this stage, ...
In the 129 family of mice, the Dnd1Ter mutation significantly increases occurrence of TGCT-affected males. To test the hypothesis that he Dnd1Ter allele is a loss-of-function mutation; we characterized the consequences of a genetically-engineered loss-of-function mutation in mice, and compared ...
p53 is mutated in over half of human cancers. In addition to losing wild-type (WT) tumor-suppressive function, mutant p53 proteins are proposed to acquire gain-of-function (GOF) activity, leading to novel oncogenic phenotypes. To study mutant p53 GOF mec
p53 partial loss-of-function mutations sensitize to chemotherapy ArticleOpen access14 December 2021 Introduction Mutation ofTP53is one of the most frequent genomic alterations in human tumors.TP53encodes p53, a sequence-specific transcription factor that regulates gene expression involved in numerous cellula...