RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response

Abstract

A proper DNA damage response (DDR), which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such as p21WAF1, BAX, and PUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage.

DNA damage stress induces the expression of Ribosomal Protein S27a gene in a p53-dependent manner

“…This might contribute towards p53 stabilization and induction of apoptotic signaling pathway (Fig. S3) (Ozaki et al, 2013). Therefore, the elevated levels of RPS27a in healthy hepatocytes may impart a role in the active action of an auto-feedback regulatory loop of p53 where its induction following DNA damage could activate RPS27a and strengthen p53 signaling.…”

DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features

“…CDKN2D is a tumor-suppressor gene in B-cell malignancies 41 and specifically inhibits CDK4 and CDK6, 42 which were upregulated in High-M SMZL. Members of the RUNX and GADD45 gene families (RUNX1/3, GADD45B/G), which cooperate with p53 in the p53-dependent response to DNA damage, 43,44 were also downregulated in the High-M cluster and, furthermore, GADD45G was highly methylated. Thus, methylation-mediated silencing of cell cycle-and DNA damage-related genes appeared to be frequent events in High-M SMZL.…”

Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association

“…The studies with the human primary OECs also revealed that P. gingivalis infection promotes a prosurvival phenotype in the host cells by accelerating the progression through the S-phase of the cell cycle via the modulation of pathways involving cyclins and p53 (Kuboniwa et al, 2008;Yilmaz, 2008). The infection by the organism is able to alter the expression of 'p53 tumor suppressor', which is known to be involved in the DNA damage response and in tumor suppression (Ozaki et al, 2013). The aforementioned actions of P. gingivalis appeared to be dependent on the presence of the major fimbriae (FimA) of the organism (Kuboniwa et al, 2008).…”