The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth

Juno Kim, Wan Namkung, Jae Seok Yoon, Min Jae Jo, Sung Hee Lee, Kyung Hwan Kim, Joo Young Kim, Min Goo Lee

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The formation of a pH gradient, which is characterized by intracellular alkalinization and extracellular acidification, plays a key role in the growth and metastasis of tumor cells. However, the underlying mechanisms of alkalinization-induced cell growth are not known. In this study, we investigated the roles of eukaryotic translation elongation factor 1 α (eEF1A) in alkalinization-induced cell growth. In all cell lines tested (NIH3T3, HEK293, and HeLa), cell growth was affected by the modulation of intracellular pH. In general, weak intracellular alkalinization produced increased cell growth, whereas intracellular acidification resulted in decreased cell growth. It is interesting to note that portions of actin-bound eEF1A proteins were gradually reduced from acidic to alkaline conditions, suggesting an increase in levels of functionally active, free-form eEF1A. Over-expression of eEF1A caused increased cell growth in HeLa cells. It should be noted that dissociation of eEF1A from actin by transfection with the actin-binding domain deleted eEF1A construct further increased cell growth under acidic conditions, whereas most of the intact eEF1A was bound to actin. Conversely, knockdown of eEF1A by treatment with eEF1A1 and eEF1A2 siRNAs nullified the effects of alkalinization-induced cell growth. The above findings suggest that an increase in free-form eEF1A under alkaline conditions plays a critical role in alkalinization-induced cell growth.

Original languageEnglish
Pages (from-to)867-874
Number of pages8
JournalLaboratory Investigation
Volume89
Issue number8
DOIs
Publication statusPublished - 2009 Aug 1

Fingerprint

Peptide Elongation Factors
Growth
Neoplasms
Actins
HeLa Cells
Peptide Elongation Factor 1
Proton-Motive Force
HEK293 Cells
Transfection
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Kim, Juno ; Namkung, Wan ; Yoon, Jae Seok ; Jo, Min Jae ; Lee, Sung Hee ; Kim, Kyung Hwan ; Kim, Joo Young ; Lee, Min Goo. / The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth. In: Laboratory Investigation. 2009 ; Vol. 89, No. 8. pp. 867-874.
@article{5e1d187ac332447ba032ea5724cc857d,
title = "The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth",
abstract = "The formation of a pH gradient, which is characterized by intracellular alkalinization and extracellular acidification, plays a key role in the growth and metastasis of tumor cells. However, the underlying mechanisms of alkalinization-induced cell growth are not known. In this study, we investigated the roles of eukaryotic translation elongation factor 1 α (eEF1A) in alkalinization-induced cell growth. In all cell lines tested (NIH3T3, HEK293, and HeLa), cell growth was affected by the modulation of intracellular pH. In general, weak intracellular alkalinization produced increased cell growth, whereas intracellular acidification resulted in decreased cell growth. It is interesting to note that portions of actin-bound eEF1A proteins were gradually reduced from acidic to alkaline conditions, suggesting an increase in levels of functionally active, free-form eEF1A. Over-expression of eEF1A caused increased cell growth in HeLa cells. It should be noted that dissociation of eEF1A from actin by transfection with the actin-binding domain deleted eEF1A construct further increased cell growth under acidic conditions, whereas most of the intact eEF1A was bound to actin. Conversely, knockdown of eEF1A by treatment with eEF1A1 and eEF1A2 siRNAs nullified the effects of alkalinization-induced cell growth. The above findings suggest that an increase in free-form eEF1A under alkaline conditions plays a critical role in alkalinization-induced cell growth.",
author = "Juno Kim and Wan Namkung and Yoon, {Jae Seok} and Jo, {Min Jae} and Lee, {Sung Hee} and Kim, {Kyung Hwan} and Kim, {Joo Young} and Lee, {Min Goo}",
year = "2009",
month = "8",
day = "1",
doi = "10.1038/labinvest.2009.53",
language = "English",
volume = "89",
pages = "867--874",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "8",

}

The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth. / Kim, Juno; Namkung, Wan; Yoon, Jae Seok; Jo, Min Jae; Lee, Sung Hee; Kim, Kyung Hwan; Kim, Joo Young; Lee, Min Goo.

In: Laboratory Investigation, Vol. 89, No. 8, 01.08.2009, p. 867-874.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth

AU - Kim, Juno

AU - Namkung, Wan

AU - Yoon, Jae Seok

AU - Jo, Min Jae

AU - Lee, Sung Hee

AU - Kim, Kyung Hwan

AU - Kim, Joo Young

AU - Lee, Min Goo

PY - 2009/8/1

Y1 - 2009/8/1

N2 - The formation of a pH gradient, which is characterized by intracellular alkalinization and extracellular acidification, plays a key role in the growth and metastasis of tumor cells. However, the underlying mechanisms of alkalinization-induced cell growth are not known. In this study, we investigated the roles of eukaryotic translation elongation factor 1 α (eEF1A) in alkalinization-induced cell growth. In all cell lines tested (NIH3T3, HEK293, and HeLa), cell growth was affected by the modulation of intracellular pH. In general, weak intracellular alkalinization produced increased cell growth, whereas intracellular acidification resulted in decreased cell growth. It is interesting to note that portions of actin-bound eEF1A proteins were gradually reduced from acidic to alkaline conditions, suggesting an increase in levels of functionally active, free-form eEF1A. Over-expression of eEF1A caused increased cell growth in HeLa cells. It should be noted that dissociation of eEF1A from actin by transfection with the actin-binding domain deleted eEF1A construct further increased cell growth under acidic conditions, whereas most of the intact eEF1A was bound to actin. Conversely, knockdown of eEF1A by treatment with eEF1A1 and eEF1A2 siRNAs nullified the effects of alkalinization-induced cell growth. The above findings suggest that an increase in free-form eEF1A under alkaline conditions plays a critical role in alkalinization-induced cell growth.

AB - The formation of a pH gradient, which is characterized by intracellular alkalinization and extracellular acidification, plays a key role in the growth and metastasis of tumor cells. However, the underlying mechanisms of alkalinization-induced cell growth are not known. In this study, we investigated the roles of eukaryotic translation elongation factor 1 α (eEF1A) in alkalinization-induced cell growth. In all cell lines tested (NIH3T3, HEK293, and HeLa), cell growth was affected by the modulation of intracellular pH. In general, weak intracellular alkalinization produced increased cell growth, whereas intracellular acidification resulted in decreased cell growth. It is interesting to note that portions of actin-bound eEF1A proteins were gradually reduced from acidic to alkaline conditions, suggesting an increase in levels of functionally active, free-form eEF1A. Over-expression of eEF1A caused increased cell growth in HeLa cells. It should be noted that dissociation of eEF1A from actin by transfection with the actin-binding domain deleted eEF1A construct further increased cell growth under acidic conditions, whereas most of the intact eEF1A was bound to actin. Conversely, knockdown of eEF1A by treatment with eEF1A1 and eEF1A2 siRNAs nullified the effects of alkalinization-induced cell growth. The above findings suggest that an increase in free-form eEF1A under alkaline conditions plays a critical role in alkalinization-induced cell growth.

UR - http://www.scopus.com/inward/record.url?scp=68149132395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68149132395&partnerID=8YFLogxK

U2 - 10.1038/labinvest.2009.53

DO - 10.1038/labinvest.2009.53

M3 - Article

VL - 89

SP - 867

EP - 874

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 8

ER -