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The fact that Emi1 overexpression promotes chromosome instability (CIN) and the formation of solid cancers in vivo indicates that Emi1 overexpression actively drives solid tumorigenesis. These novel mechanistic insights have important clinical implications.
Examined eoffect of Emi1 over-expression on Skp2 expression in breast cancer. Found expression of Emi1 was positively related with Skp2 expression; Emi1 expression correlated significantly with histologic grade. Skp2 expression obtained similar results.
Human papillomavirus type 16 E7 expression causes increased EMI1 mRNA expression and also inhibits EMI1 degradation.
The C-terminal domain inhibits multiple APC/C(CDH1) functions. The intrinsically disordered D-box, linker & tail elements, & a structured Zn-binding domain synergistically block the substrate-binding site & inhibit ubiquitin-chain elongation.
Emi1 depletion enhances the sensitivity of cancer cells to doxorubicin and x-ray irradiation.
Emi1 expression (>5%) was seen in 23.3% of ovarian clear cell carcinoma, and associated with high FIGO grades and poor overall survival
Emi1 participates in human hepatocellular carcinoma (HCC (show FAM126A Proteins)) cell proliferation and that progression is controlled by anaphase-promoting complex/cyclosome (APC (show APC Proteins)/C) inhibition, which stabilized Skp2 and enabled p27(kip1 (show CDKN1B Proteins)) degradation.
the ability of Emi1 to inhibit APC (show APC Proteins)/C is negatively regulated by CDKs
Results suggest that Bcr-Abl increases Emi1 phosphorylation and stability to prevent Skp2 protein degradation via APC/Cdh1-induced ubiquitination and to enhance proliferation of CML cells.
These data suggest that E2F (show E2F1 Proteins) can activate both transcription of cyclin A (show CCNA2 Proteins) and the hEmi1-dependent stabilization of APC (show APC Proteins)(Cdh1 (show CDH1 Proteins)) targets, such as cyclin A (show CCNA2 Proteins), to promote S phase entry.
These data indicate that emi1 deficiency-induced defects in vivo are due to the dysregulation of an APC/C-Cdh1 (show CDH1 Proteins) molecular axis.
harpy/Rca1/emi1 has a role in patterning in the absence of cell division
Emi1 is a critical regulator of genomic fidelity during embryogenesis.
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Alternatively spliced transcript variants encoding different isoforms have been identified.
F-box only protein 5
, F-box protein Fbx5
, early mitotic inhibitor 1
, f-box only protein 31