EphrinB1: Novel microtubule associated protein whose expression affects taxane sensitivity

Paul L. Colbert, Daniel W. Vermeer, Bryant G. Wieking, John H. Lee, Paola D. Vermeer

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)953-968
Number of pages16
JournalOncotarget
Volume6
Issue number2
DOIs
StatePublished - Jan 1 2015

Fingerprint

Microtubule-Associated Proteins
Microtubules
Tubulin
Mitosis
Cell Cycle
Protein Tyrosine Phosphatases
Cytokinesis
Oncogene Proteins
Infection
Cytoskeleton
Phosphoric Monoester Hydrolases
Neoplasms
Homeostasis
Phosphorylation
Cell Proliferation
Phenotype
Mutation
taxane

Keywords

  • EphrinB1
  • Microtubule
  • Mitosis
  • PTPN13
  • Taxane

ASJC Scopus subject areas

  • Oncology

Cite this

EphrinB1 : Novel microtubule associated protein whose expression affects taxane sensitivity. / Colbert, Paul L.; Vermeer, Daniel W.; Wieking, Bryant G.; Lee, John H.; Vermeer, Paola D.

In: Oncotarget, Vol. 6, No. 2, 01.01.2015, p. 953-968.

Research output: Contribution to journalArticle

Colbert, Paul L. ; Vermeer, Daniel W. ; Wieking, Bryant G. ; Lee, John H. ; Vermeer, Paola D. / EphrinB1 : Novel microtubule associated protein whose expression affects taxane sensitivity. In: Oncotarget. 2015 ; Vol. 6, No. 2. pp. 953-968.
@article{2bf3b8f2c9b147f683cd3fe1f41811f4,
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.",
keywords = "EphrinB1, Microtubule, Mitosis, PTPN13, Taxane",
author = "Colbert, {Paul L.} and Vermeer, {Daniel W.} and Wieking, {Bryant G.} and Lee, {John H.} and Vermeer, {Paola D.}",
year = "2015",
month = "1",
day = "1",
doi = "10.18632/oncotarget.2823",
language = "English (US)",
volume = "6",
pages = "953--968",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "2",

}

TY - JOUR

T1 - EphrinB1

T2 - Novel microtubule associated protein whose expression affects taxane sensitivity

AU - Colbert, Paul L.

AU - Vermeer, Daniel W.

AU - Wieking, Bryant G.

AU - Lee, John H.

AU - Vermeer, Paola D.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - EphrinB1

KW - Microtubule

KW - Mitosis

KW - PTPN13

KW - Taxane

UR - http://www.scopus.com/inward/record.url?scp=84921713197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921713197&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.2823

DO - 10.18632/oncotarget.2823

M3 - Article

C2 - 25436983

AN - SCOPUS:84921713197

VL - 6

SP - 953

EP - 968

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 2

ER -