High impact information on EVI5

• Evi5 antagonizes SCF(betaTrCP)-dependent Emi1 ubiquitination and destruction by binding to a site adjacent to Emi1's DSGxxS degron and blocking both degron phosphorylation by Polo-like kinases and subsequent betaTrCP binding [1].
• The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1 [1].
• Identification of Rab11 as a small GTPase binding protein for the Evi5 oncogene [2].
• Indeed, ablation of Evi5 by RNA interference causes a mislocalization of FIP3 at the abscission site during cytokinesis [2].
• Here we describe the identification of Evi5 as a candidate binding protein for Rab11, a GTPase that regulates intracellular transport and has specific roles in endosome recycling and cytokinesis [2].

Biological context of EVI5

• FPLC analysis demonstrates that EVI5 protein can form dimers and confocal microscopy indicates that EVI5, in addition to a diffuse localization in the nucleus, also preferentially localizes to the pericentriolar material in interphase cells [3].
• EVI5 is ubiquitously expressed in adult, fetal, and cancer tissues and exists as two mRNA species resulting from differential use of polyadenylation signals [3].
• Knockdown of EVI5 using siRNA results in a multinucleate phenotype, which is consistent with an essential role for this protein in the completion of cytokinesis [4].
• Together, these data provide evidence that EVI5 is an essential component of the protein machinery facilitating the final stages of cell septation at the end of mitosis [4].
• The EVI5 protein also undergoes posttranslational modifications during the cell cycle, which involve phosphorylation in early mitosis and proteolytic cleavage during late mitosis and cytokinesis [4].

Anatomical context of EVI5

• Thus, EVI5 is a novel centrosomal protein with a complex expression pattern and subcellular localization, possibly involved in centrosome stability and dynamics [3].

Other interactions of EVI5

• The human EVI5 protein carries a TBC domain indicative of Rab GTPase activating protein (GAP) activity, and an extensive coiled-coil motif in the C-terminal region [3].
• EVI5 protein associates with the INCENP-aurora B kinase-survivin chromosomal passenger complex and is involved in the completion of cytokinesis [4].

Analytical, diagnostic and therapeutic context of EVI5

• Immunoprecipitation and GST pull-down experiments demonstrate that EVI5 exists in complexes with both alpha- and gamma-tubulin [3].
• In this report, we demonstrate using immunofluorescence microscopy that EVI5 has a dynamic distribution during mitosis, being associated with the mitotic spindle through anaphase and remaining within the midzone and midbody until completion of cytokinesis [4].

References