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A subset of BRCA1-deficient triple-negative breast cancer cells develop resistance to PARP inhibitors by downregulating EMI1 and restoring RAD51-dependent HRR. Reconstitution of EMI1 expression reestablishes PARPi sensitivity both in cellular systems and in an orthotopic mouse model.
demonstration using human cell models that cell-cycle commitment is mediated by an EMI1-APC/C(CDH1) dual-negative feedback switch, in which EMI1 is both a substrate and an inhibitor of APC/C(CDH1)
Both isoforms of FBXO5 promoted the migration and osteogenic differentiation potential of human periodontal ligament stem cells.
Results from a study on gene variability markers in early-stage human embryos shows that FBXO5 is a putative variability marker for the 3-day, 8-cell embryo stage.
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) cell proliferation and that progression is controlled by anaphase-promoting complex/cyclosome (APC/C) inhibition, which stabilized Skp2 and enabled p27(kip1) degradation.
the ability of Emi1 to inhibit APC/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 can activate both transcription of cyclin A and the hEmi1-dependent stabilization of APC(Cdh1) targets, such as cyclin A, to promote S phase entry.
Plk1 activates the anaphase promoting complex by directing the SCF-dependent destruction of Emi1 in prophase
loss of pRb repression of E2F-mediated transcription causing misregulation of Emi1 and APC/C substrates results in the generation of tetraploidy and proliferation of genomically unstable cells in the absence of normal p53 function
Emi1 associates in a complex with the anaphase-promoting complex/cyclosome (APC/C) and Cdh1; Emi1 binds to the APC/C via a conserved C-terminal destruction (D)-box and can compete for APC/C-substrate interaction.
bservations reveal a novel mechanism for the control of entry into the first meiotic division: an Emi1-dependent inhibition of APC(Cdh1).
These data suggest that Emi1 plays a critical role in preserving genome integrity by blocking rereplication, revealing a previously unrecognized function of this inhibitor of anaphase-promoting complex/cyclosome.
Emi1 plays a crucial role in the cell cycle to couple DNA replication with mitosis
These data indicate that emi1 deficiency-induced defects in vivo are due to the dysregulation of an APC/C-Cdh1 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