Another study has highlighted the efficiency of UHRF1 as a marker to differentially diagnose pancreatic adenocarcinoma, chronic pancreatitis and normal pancreas [38]. UHRF1 over-GSK2245840 expression was also found in bladder cancer and the intensity of its over-expression appears to be related to the stage of the cancer [39], suggesting that the presence of UHRF1 in urine

sediment or surgical specimens could be a useful diagnostic marker and may improve the diagnosis of the bladder cancer. Recently, UHRF1′s overpression has also been described in lung cancer cells, particularly https://www.selleckchem.com/products/OSI-906.html in non-adenocarcinomas [40]. This alteration in UHRF1 expression could be linked to the degree of the lung cancer aggressiveness and was detectable in half of the patients in an early pathological stage. This suggests therefore that UHRF1 could be a novel diagnostic tool for lung cancer [40]. Altogether, these clinical studies show that immuno-histochemical staining of UHRF1 may improve the specificity and sensitivity of current tests Pevonedistat price for cancer diagnosis. These studies also emphasize that over-expression of UHRF1 might be involved in the establishment of aberrant histone code

and altered DNA methylation patterns. The consequences of UHRF1 over-expression are cell contact inhibition loss [41] and inhibition of TSGs expression, such as CDKN2A and RASSF1 [42]. Furthermore, very recently, it was shown that UHRF1 down-regulation in p53 containing and

deficient cancer cells induced cell cycle arrest in G2/M and caspase-8-dependent apoptosis [43]. This is consistent with previous studies showing that down-regulation of UHRF1 leads to cell growth inhibition [44–46]. UHRF1 is characterized by the presence of several structural domains, CHIR-99021 cost some facing DNA and others facing histones (Figure 1). Among them, one of the most amazing domain is undoubtedly the SRA domain (Set and Ring Associated) which, in vertebrates, is found only in the UHRF family [35]. Thanks to this domain, UHRF1 interacts with histone deacetylase 1 (HDAC1) and can bind to methylated promoter regions of various TSGs, including p16 INK4A and p14 ARF [44]. Moreover, we have shown that UHRF1, via the SRA domain, associates with DNA methyltransferase 1 (DNMT1) to form a couple cooperating in the duplication of the DNA methylation patterns but other domains of UHRF1 could also be involved [26, 47–49]. The mechanism of DNA methylation pattern duplication, involves the SRA domain which is able to detect the hemi-methylated state of the DNA that occurs after the synthesis of the new DNA strand [50–52]. This domain behaves as a “”hand”" with a palm which holds the methylated cytosine, after that two “”fingers”" have flipped the methylated cytosine out from the DNA helix into the major DNA groove.