High-risk human papillomavirus oncoproteins E6 and E7 play a major role in HPV-related cancers. One of the main functions of E7 is the degradation of pRb, while E6 promotes the degradation of p53, inactivating the p14ARF-p53 pathway. pRb and p14ARF can repress ribosomal DNA (rDNA) transcription in part by targeting the Upstream Binding Factor 1 (UBF1), a key factor in the activation of RNA poly...

p14ARF tumour suppressor stabilises and activates p53 by directly interacting with (H)Mdm2 [(human) murine double minute 2 homologue] and inhibiting its E3 ubiquitin ligase activity. Here we demonstrate that p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1. Mutational analysis demonstrated that the N-terminus of Mdm2 is a target for p14ARF-mediated S...

The INK4a/ARF locus encodes two distinct tumor suppressors, p16INK4a and p14ARF. Although the contribution of p16INK4a to human tumorigenesis through point mutation, deletion, and hypermethylation has been widely documented, little is known about specific p14ARF lesions and their consequences. Recent data indicate that p14ARF suffers inactivation by promoter hypermethylation in colorectal cance...

BACKGROUND Primary liver cancer is a common malignant tumor that causes serious damage to human health. DNA methylation is common in epigenetics. DNA methylation plays an important role in the process of primary liver cancer occurrence and development. The P14ARF gene is an important tumor suppressor gene. It was found that P14ARF methylation is associated with the degree of malignancy in multi...

Purpose and Experimental Design: The molecular mechanisms by which the p14ARF gene is altered in non–small cell lung cancer (NSCLC) are complex and unclear. Using genetic and epigenetic analyses, we examined various molecular alterations including the loss of protein and mRNA expression, and 5 CpG hypermethylation, allelic imbalance, and mutation of the p14ARF gene in a series of 102 NSCLC samp...

The goal of this study was to clarify the role p16INK4a, p14ARF, and p53 protein expressions in carcinogenesis squamous cell carcinomas lip. p53, p14ARF proteins were examined 46 formaline-fixed paraffin embedded tissue specimens, which included 19 cases carcinoma lip, 14 actinic cheilitis, 13 normal mucosa. Immunoreactivity peritumoral epithelium adjacent als

The present study examined the effect of the overexpression of early growth response gene (Egr-1) on transforming growth factor β-1 (TGF-β1) and p14ARF levels, in PC-3 and LNCaP prostate carcinoma cell lines. Amplification of EGR-1, TGF-β1 and p14ARF were observed in the two cell lines treated with different stimuli and resulted in a corresponding mRNA and protein expression. The downregulation...

The N-terminal tail of histone H2B is believed to be involved in gene silencing, but how it exerts its function remains elusive. Here, we report the biochemical characterization of p14ARF tumor suppressor as a transcriptional repressor that selectively recognizes the unacetylated H2B tails on nucleosomes. The p14ARF-H2B tail interaction is functional, as the antagonistic effect of p14ARF on chr...

As part of a cell's inherent protection against carcinogenesis, p14ARF is upregulated in response to hyperproliferative signalling to induce cell cycle arrest. This property makes p14ARF a leading candidate for cancer therapy. This study explores the consequences of reactivating p14ARF in breast cancer and the potential of targeting p14ARF in breast cancer treatment. Our results show that activ...

Overexpression of E2F-1 induces apoptosis by both a p14ARF-p53- and a p73-mediated pathway. p14ARF is the alternate tumor suppressor product of the INK4a/ARF locus that is inactivated frequently in lung carcinogenesis. Because p14ARF stabilizes p53, it has been proposed that the loss of p14ARF is functionally equivalent to a p53 mutation. We have tested this hypothesis by examining the genomic ...