title: The role of the two splice variants and extranuclear pathway on Ki-67 regulation in non-cancer and cancer cells.
abstract: Ki-67 is a nuclear protein that has been used in cancer diagnostic because of its specific cell-cycle dependent expression profile. After quantifying and characterising the expression level of Ki-67, as a function of the cell cycle, we found out that the two main splice variants of the protein (i.e. α and β) are differently regulated in non-cancerous and cancerous cells both at mRNA and protein level. We were able to correlate the presence of the α variant of the protein with the progression through the interphase of cell cycle. We also observed that the different expression profiles correspond to different degradation pathways for non-cancerous and cancerous cells. Furthermore, Ki-67 is continuously regulated and degraded via proteasome system in both cell types, suggesting an active control of the protein. However we also observed a putative extranuclear elimination pathway of Ki-67 where it is transported to the Golgi apparatus. Our evidence in the different expression of the splice variants may represent a milestone for the development of new targets for cancer diagnostic and prognostic. Additionally, the unexpected extranuclear elimination of Ki-67 strongly suggests that this protein must be looked at also outside of the "nuclear box", as thought to date.
authors.affiliation: Department of Chemistry, University College London, London, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Chierico
authors.affiliation: Department of Chemistry, University College London, London, United Kingdom.
authors.forename: Loris
authors.initials: L
authors.lastname: Rizzello
authors.affiliation: Department of Chemistry, University College London, London, United Kingdom.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Chemistry, University College London, London, United Kingdom.
authors.forename: Adrian Steve
authors.initials: AS
authors.lastname: Joseph
authors.affiliation: Biocompatibles UK Ltd., Farnham Business Park, Weydon Lane, Farnham, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lewis
authors.affiliation: Department of Chemistry, University College London, London, United Kingdom.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
mesh_terms: D017398:Alternative Splicing; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport
chemical_list: D019394:Ki-67 Antigen; D046988:Proteasome Endopeptidase Complex