C-Raf antagonizes apoptosis induced by IFN-α in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A

A. Lamberti, O. Longo, M. Marra, P. Tagliaferri, E. Bismuto, A. Fiengo, C. Viscomi, A. Budillon, U. R. Rapp, E. Wang, S. Venuta, A. Abbruzzese, P. Arcari, M. Caraglia

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Interferon α (IFNα) induces both apoptosis and a counteracting epidermal growth factor Erk-dependent survival response in cancer cells. In this report, IFNα increased eukaryotic elongation factor 1A (eEF-1A) protein expression by inhibition of eEF-1A degradation via a proteasome-dependent pathway. The reduction of the expression level of eEF-1A by RNA interference enhanced the apoptosis induced by IFNα on the same cells. Moreover, IFNα induced the phosphorylation of both serine and threonine in eEF-1A. These effects were paralleled by an increased co-immunoprecipitation and colocalization of eEF-1A with C-Raf. The suppression of C-Raf kinase activity with the inhibitor BAY 43-9006 completely antagonized the increase of both eEF-1A phosphorylation and expression and of C-Raf/ eEF-1A colocalization induced by IFNα and enhanced apoptosis and eEF-1A ubiquitination. Cell transfection with the mutated K48R ubiquitin increased EF-1A expression and desensitized tumor cells to the modulating effects of IFNα. The dynamic simulation of 3Dstructure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity.

Original languageEnglish
Pages (from-to)952-962
Number of pages11
JournalCell Death and Differentiation
Volume14
Issue number5
DOIs
Publication statusPublished - May 2007

Fingerprint

Peptide Elongation Factors
Interferons
Lung Neoplasms
Phosphorylation
Apoptosis
Threonine
Serine
raf Kinases
Survival
Ubiquitination
Proteasome Endopeptidase Complex
Ubiquitin
RNA Interference
Immunoprecipitation
Epidermal Growth Factor
Transfection
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

C-Raf antagonizes apoptosis induced by IFN-α in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A. / Lamberti, A.; Longo, O.; Marra, M.; Tagliaferri, P.; Bismuto, E.; Fiengo, A.; Viscomi, C.; Budillon, A.; Rapp, U. R.; Wang, E.; Venuta, S.; Abbruzzese, A.; Arcari, P.; Caraglia, M.

In: Cell Death and Differentiation, Vol. 14, No. 5, 05.2007, p. 952-962.

Research output: Contribution to journalArticle

Lamberti, A, Longo, O, Marra, M, Tagliaferri, P, Bismuto, E, Fiengo, A, Viscomi, C, Budillon, A, Rapp, UR, Wang, E, Venuta, S, Abbruzzese, A, Arcari, P & Caraglia, M 2007, 'C-Raf antagonizes apoptosis induced by IFN-α in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A', Cell Death and Differentiation, vol. 14, no. 5, pp. 952-962. https://doi.org/10.1038/sj.cdd.4402102
Lamberti, A. ; Longo, O. ; Marra, M. ; Tagliaferri, P. ; Bismuto, E. ; Fiengo, A. ; Viscomi, C. ; Budillon, A. ; Rapp, U. R. ; Wang, E. ; Venuta, S. ; Abbruzzese, A. ; Arcari, P. ; Caraglia, M. / C-Raf antagonizes apoptosis induced by IFN-α in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A. In: Cell Death and Differentiation. 2007 ; Vol. 14, No. 5. pp. 952-962.
@article{e6a15808193c4584b8f1be0a4bd4e2d2,
title = "C-Raf antagonizes apoptosis induced by IFN-α in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A",
abstract = "Interferon α (IFNα) induces both apoptosis and a counteracting epidermal growth factor Erk-dependent survival response in cancer cells. In this report, IFNα increased eukaryotic elongation factor 1A (eEF-1A) protein expression by inhibition of eEF-1A degradation via a proteasome-dependent pathway. The reduction of the expression level of eEF-1A by RNA interference enhanced the apoptosis induced by IFNα on the same cells. Moreover, IFNα induced the phosphorylation of both serine and threonine in eEF-1A. These effects were paralleled by an increased co-immunoprecipitation and colocalization of eEF-1A with C-Raf. The suppression of C-Raf kinase activity with the inhibitor BAY 43-9006 completely antagonized the increase of both eEF-1A phosphorylation and expression and of C-Raf/ eEF-1A colocalization induced by IFNα and enhanced apoptosis and eEF-1A ubiquitination. Cell transfection with the mutated K48R ubiquitin increased EF-1A expression and desensitized tumor cells to the modulating effects of IFNα. The dynamic simulation of 3Dstructure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity.",
author = "A. Lamberti and O. Longo and M. Marra and P. Tagliaferri and E. Bismuto and A. Fiengo and C. Viscomi and A. Budillon and Rapp, {U. R.} and E. Wang and S. Venuta and A. Abbruzzese and P. Arcari and M. Caraglia",
year = "2007",
month = "5",
doi = "10.1038/sj.cdd.4402102",
language = "English",
volume = "14",
pages = "952--962",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - C-Raf antagonizes apoptosis induced by IFN-α in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A

AU - Lamberti, A.

AU - Longo, O.

AU - Marra, M.

AU - Tagliaferri, P.

AU - Bismuto, E.

AU - Fiengo, A.

AU - Viscomi, C.

AU - Budillon, A.

AU - Rapp, U. R.

AU - Wang, E.

AU - Venuta, S.

AU - Abbruzzese, A.

AU - Arcari, P.

AU - Caraglia, M.

PY - 2007/5

Y1 - 2007/5

N2 - Interferon α (IFNα) induces both apoptosis and a counteracting epidermal growth factor Erk-dependent survival response in cancer cells. In this report, IFNα increased eukaryotic elongation factor 1A (eEF-1A) protein expression by inhibition of eEF-1A degradation via a proteasome-dependent pathway. The reduction of the expression level of eEF-1A by RNA interference enhanced the apoptosis induced by IFNα on the same cells. Moreover, IFNα induced the phosphorylation of both serine and threonine in eEF-1A. These effects were paralleled by an increased co-immunoprecipitation and colocalization of eEF-1A with C-Raf. The suppression of C-Raf kinase activity with the inhibitor BAY 43-9006 completely antagonized the increase of both eEF-1A phosphorylation and expression and of C-Raf/ eEF-1A colocalization induced by IFNα and enhanced apoptosis and eEF-1A ubiquitination. Cell transfection with the mutated K48R ubiquitin increased EF-1A expression and desensitized tumor cells to the modulating effects of IFNα. The dynamic simulation of 3Dstructure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity.

AB - Interferon α (IFNα) induces both apoptosis and a counteracting epidermal growth factor Erk-dependent survival response in cancer cells. In this report, IFNα increased eukaryotic elongation factor 1A (eEF-1A) protein expression by inhibition of eEF-1A degradation via a proteasome-dependent pathway. The reduction of the expression level of eEF-1A by RNA interference enhanced the apoptosis induced by IFNα on the same cells. Moreover, IFNα induced the phosphorylation of both serine and threonine in eEF-1A. These effects were paralleled by an increased co-immunoprecipitation and colocalization of eEF-1A with C-Raf. The suppression of C-Raf kinase activity with the inhibitor BAY 43-9006 completely antagonized the increase of both eEF-1A phosphorylation and expression and of C-Raf/ eEF-1A colocalization induced by IFNα and enhanced apoptosis and eEF-1A ubiquitination. Cell transfection with the mutated K48R ubiquitin increased EF-1A expression and desensitized tumor cells to the modulating effects of IFNα. The dynamic simulation of 3Dstructure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity.

UR - http://www.scopus.com/inward/record.url?scp=34247324325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247324325&partnerID=8YFLogxK

U2 - 10.1038/sj.cdd.4402102

DO - 10.1038/sj.cdd.4402102

M3 - Article

C2 - 17332776

AN - SCOPUS:34247324325

VL - 14

SP - 952

EP - 962

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 5

ER -