The ubiquitin-recognition protein Ufd1 facilitates clearance of misfolded proteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. Here we report that prolonged ER stress represses Ufd1 expression to trigger cell cycle delay, which contributes to ERAD. Remarkably, down-regulation of Ufd1 enhances ubiquitination and destabilization of Skp2 mediated by the anaphase-p...

The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system was previously unknown. We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth. Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat cerebellum in vivo revealed cell-autonomous abnormalities in layer-specific gro...

Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15-50 % of affected kindred that meet the clinical criteria for HDGC. If any of the criteria is met the individual is referred to genetic counseling and CDH1 testing is offered. In this report we present the case of a Spanish family with HDG...

BACKGROUND Primary gastric B-cell lymphomas arise from mucosa-associated lymphatic tissue (MALT) in patients with chronic Helicobacter pylori infection. We investigated whether germline variants in the CDH1 gene, coding for E-cadherin, genetically predispose patients to primary gastric B-cell lymphoma. DESIGN AND METHODS Single marker analyses of the CDH1 gene were conducted in patients with ...

OBJECTIVE To screen and characterize germline variants for E-cadherin (CDH1) in non-hereditary gastric cancer (GC) patients and in subjects at risk of GC. METHODS 59 GCs, 59 first degree relatives (FDRs) of GC, 20 autoimmune metaplastic atrophic gastritis (AMAGs) and 52 blood donors (BDs) were analyzed for CDH1 by direct sequencing, structural modelling and bioinformatics. Functional impact o...

Bone morphogenic protein (BMP) signalling contributes towards maintenance of pluripotency and favours mesodermal over neural fates upon differentiation, but the mechanisms by which BMP controls differentiation are not well understood. We report that BMP regulates differentiation by blocking downregulation of Cdh1, an event that accompanies the earliest stages of neural and mesodermal differenti...

The anaphase-promoting complex/cyclosome (APC/C) regulates sister chromatid segregation and the exit from mitosis. Selection of most APC/C substrates is controlled by coactivator subunits (either Cdc20 or Cdh1) that interact with substrate destruction motifs--predominantly the destruction (D) box and KEN box degrons. How coactivators recognize D box degrons and how this is inhibited by APC/C re...

BACKGROUND Most gastric cancer (GC) is sporadic and seem to be mostly related to a cumulative effect of multiple environmental factors. Although the actual importance of genetic factors has not yet been fully documented, GC with familial aggregation has been found to have an incidence of 10% to 30%. MATERIALS AND METHODS Genetic factors contribute to the well-known autosomal dominant syndrome...

  Absract   Gastric cancer is the fourth most common cancer and the second leading cause of   cancer death. Most cases are sporadic and only 10% of patients, show familial clustering. Among these patients, 1 to 3 % have hereditary diffuse gastric cancer   (HDGC), which is autosomal-dominant and present in younger ages. Mutations in Ecadherin gene CDH1 has been identified in 30 to 50% of patient...

In this study, we examined the effect of a combination surface topographies (fiber alignments) and different stiffness poly(L-lactic acid) (PLLA) substrates on direct relationship between anti-cancer drug (CDDP) sensitivity for MDA-MB-231 cells mesenchymal properties under both normal hypoxic conditions. addition, studied induction epithelial–mesenchymal transition (EMT). The CDDP treatment hyp...