Disease relevance of FZR1

• BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is defined by germline mutations in the E-cadherin gene, CDH-1 [1].
• One of the genes residing within SRO2 is the E-cadherin gene, CDH1, which has previously been shown to be mutated in lobular breast carcinomas, resulting in loss of E-cadherin expression [2].
• Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples [3].

High impact information on FZR1

• The DNA damage-induced mitotic exit delay correlates with the inhibition of Cdh1 activation and the attenuated degradation of cyclin B1 [4].
• Direct evidence of E-cadherin mutations triggering tumorigenesis has come from the finding of inactivating germline mutations of the gene (CDH1) in hereditary diffuse gastric cancer (HDGC) [5].
• In this study we investigated the importance of periodic oscillation of the APC-Cdh1 activity for the cell cycle progression in human cells [6].
• Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis [6].
• Consequently, failure to inactivate APC-Cdh1 beyond the G(1)/S transition not only inhibited productive cell division but also supported slow but uninterrupted DNA replication, precluding S-phase exit and causing massive overreplication of the genome [6].

Biological context of FZR1

• Although the role of the APC in mitosis is relatively clear, there is mounting evidence that APCs containing Cdh1 (APC(CDH1)) also have a function in the G1 phase of the cell cycle [7].
• Immunohistochemistry showed a significant association between CDH1 methylation and E-cadherin expression (P < 0.001) [8].
• LOH of CDH1 gene was found in 57.1% of NEECs but only in 22.5% of EECs (p = 0.011) and showed a trend towards association with reduced E-cadherin expression (p = 0.089) [9].
• CDH1 gene at human chromosome 16q22.1 encodes E-cadherin [10].
• Alterations in the gene CDH1 on chromosome 16q22 are associated with changes in E-cadherin protein expression and function [11].

Anatomical context of FZR1

• BACKGROUND: The CDH1 gene encodes E-cadherin, an epithelial cell adhesion molecule [12].

Associations of FZR1 with chemical compounds

• The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1 [13].

References