RNF43 interacts with NEDL1 and regulates p53-mediated transcription

Abstract

The ubiquitin-proteasomal system plays a crucial role in oncogenesis in colorectal tissues. Recent studies have shown that stability of -catenin, which functions as an oncogene for colorectal cancer, is regulated by ubiquitin-mediated degradation. It has been reported that a putative E3 ubiquitin ligase, RNF43, is highly expressed in human colorectal carcinoma and that RNF43 promotes cell growth. However, the involvement of RNF43 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that RNF43 binds to NEDD-4-like ubiquitin-protein ligase-1 (NEDL1), which enhances pro-apoptotic activity by p53. In addition, we found that RNF43 also interacts with p53 and that RNF43 suppresses transcriptional activity of p53 in H1299 cells and attenuates apoptosis induced by ultraviolet irradiation. These findings suggest that RNF43 is associated with p53-mediated apoptosis in collaboration with NEDL1 in colorectal carcinogenesis.3

Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways

“…RNF43, genetically inactivated in both types of mucinous cysts (IPMNs and MCNs), has intrinsic E3 ubiquitin ligase activity (46). There has been relatively little research on this gene's product, although it has been shown to be present in a complex that regulates p53-mediated apoptosis (60). Based on these past studies, it is likely that the tumor suppressor effects of the WT RNF43 gene product are a result of its ubiquitin ligase activity.…”

Genetic Association of Short Sleep Duration With Hypertension Incidence

“…39 The present study showed that women sleeping less than 5 h per night had a significantly higher triglyceride level than women sleeping 5-7 h per night. JMJD2A, 40 THSD4, 41 LOC440142, 42 and RNF43 43 have not been previously known to have relationships with BP or HT. Although gene-environment interactions play an important role in HT, the predictive power of genetic variants is still unclear for incident HT.…”

Reversing Effect of Ring Finger Protein 43 Inhibition on Malignant Phenotypes of human Hepatocellular Carcinoma

“…regulate the G 1 -S transition of cell cycle, matched well with the decreased proliferative status, suggesting that knockdown of RNF43 attenuates the activation of cyclincdk complexes and therefore inhibit the proliferation of HCCs. It is noteworthy that RNF43 has been reported to be implicated in p53-mediated apoptosis (9). In our study, the expression level of p53 was higher after RNF43 inhibition, suggesting that RNF43 knockdown induces HCC apoptosis, at least in part, via p53-dependent pathway.…”

“…Although it has been proven that RNF43 is highly expressed in colorectal carcinoma and acts as an oncogene in colon cancer cells (8,9), its role in HCCs has not been reported. Here, we found that RNF43 was frequently overexpressed in HCCs tissues and cell lines, and its overexpression was correlated with positive vascular invasion, poor tumor differentiation, and advanced tumor stage, suggesting that increased expression of RNF43 may contribute to the progression of HCCs.…”

“…Forced overexpression of RNF43 has been shown to promote the growth of colon cancer cells, whereas knockdown of RNF43 retarded this growth (8). Besides its growth-promoting effect, RNF43 also interacts with NEDL1, an upstream p53 regulator, thereby inhibiting the transcriptional and pro-apoptotic activity of p53 (9). Moreover, RNF43 could form structural complexes with PSF/p54nrb and HAP95 (10,11), but the biologic relevance of these physical interactions has not yet been proven.…”