title: EphrinB1: novel microtubule associated protein whose expression affects taxane sensitivity.
abstract: Microtubules (MTs) are components of the cytoskeleton made up of polymerized alpha and beta tubulin dimers. MT structure and function must be maintained throughout the cell cycle to ensure proper execution of mitosis and cellular homeostasis. The protein tyrosine phosphatase, PTPN13, localizes to distinct compartments during mitosis and cytokinesis. We have previously demonstrated that the HPV16 E6 oncoprotein binds PTPN13 and leads to its degradation. Thus, we speculated that HPV infection may affect cellular proliferation by altering the localization of a PTPN13 phosphatase substrate, EphrinB1, during mitosis. Here we report that EphrinB1 co-localizes with MTs during all phases of the cell cycle. Specifically, a cleaved, unphosphorylated EphrinB1 fragment directly binds tubulin, while its phosphorylated form lacks MT binding capacity. These findings suggest that EphrinB1 is a novel microtubule associated protein (MAP). Importantly, we show that in the context of HPV16 E6 expression, EphrinB1 affects taxane response in vitro. We speculate that this reflects PTPN13's modulation of EphrinB1 phosphorylation and suggest that EphrinB1 is an important contributor to taxane sensitivity/resistance phenotypes in epithelial cancers. Thus, HPV infection or functional mutations of PTPN13 in non-viral cancers may predict taxane sensitivity.
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Colbert
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Vermeer
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA.
authors.forename: Bryant G
authors.initials: BG
authors.lastname: Wieking
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA.
authors.forename: Paola D
authors.initials: PD
authors.lastname: Vermeer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D036387:Ephrin-B1 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D052163:Human papillomavirus 6 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D061986:MCF-7 Cells; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D011485:Protein Binding; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; C068651:E6 protein, Human papillomavirus type 16; D036387:Ephrin-B1; D008869:Microtubule-Associated Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel