Nucleolin enhances internal ribosomal entry site (IRES)-mediated translation of Sp1 in tumorigenesis

Chia Yang Hung, Wen Bin Yang, Shao An Wang, Tsung I. Hsu, Wen Chang Chang, Jan Jong Hung

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Our previous study indicated that specificity protein-1 (Sp1) is accumulated during hypoxia in an internal ribosomal entry site (IRES)-dependent manner. Herein, we found that the Sp1 was induced strongly at the protein level, but not in the mRNA level, in lung tumor tissue, indicating that translational regulation might contribute to the Sp1 accumulation during tumorigenesis. A further study showed that the translation of Sp1 was dramatically induced through an IRES-dependent pathway. RNA immunoprecipitation analysis of proteins bound to the 5'-untranslated region (5'-UTR) of Sp1 identified interacting protein - nucleolin. Knockdown of nucleolin significantly inhibited IRES-mediated translation of Sp1, suggesting that nucleolin positively facilitates Sp1 IRES activation. Further analysis of the interaction between nucleolin and the 5'-UTR of Sp1 mRNA revealed that the GAR domain was important for IRES-mediated translation of Sp1. Moreover, gefitinib, and LY294002 and MK2206 compounds inhibited IRES-mediated Sp1 translation, implying that activation of the epithelial growth factor receptor (EGFR) pathway via Akt activation triggers the IRES pathway. In conclusion, EGFR activation-mediated nucleolin phosphorylated at Thr641 and Thr707 was recruited to the 5'-UTR of Sp1 as an IRES trans-acting factor to modulate Sp1 translation during lung cancer formation.

Original languageEnglish
Pages (from-to)2843-2854
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number12
DOIs
Publication statusPublished - Aug 27 2014

Fingerprint

Protein Biosynthesis
Carcinogenesis
Proteins
5' Untranslated Regions
Growth Factor Receptors
nucleolin
Messenger RNA
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Trans-Activators
Immunoprecipitation
Lung Neoplasms
RNA
Lung

Keywords

  • EGFR
  • IRES
  • Nucleolin
  • Phosphorylation
  • Sp1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Nucleolin enhances internal ribosomal entry site (IRES)-mediated translation of Sp1 in tumorigenesis. / Hung, Chia Yang; Yang, Wen Bin; Wang, Shao An; Hsu, Tsung I.; Chang, Wen Chang; Hung, Jan Jong.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1843, No. 12, 27.08.2014, p. 2843-2854.

Research output: Contribution to journalArticle

@article{cfd5a58830b64a54b03c3c056a65f149,
title = "Nucleolin enhances internal ribosomal entry site (IRES)-mediated translation of Sp1 in tumorigenesis",
abstract = "Our previous study indicated that specificity protein-1 (Sp1) is accumulated during hypoxia in an internal ribosomal entry site (IRES)-dependent manner. Herein, we found that the Sp1 was induced strongly at the protein level, but not in the mRNA level, in lung tumor tissue, indicating that translational regulation might contribute to the Sp1 accumulation during tumorigenesis. A further study showed that the translation of Sp1 was dramatically induced through an IRES-dependent pathway. RNA immunoprecipitation analysis of proteins bound to the 5'-untranslated region (5'-UTR) of Sp1 identified interacting protein - nucleolin. Knockdown of nucleolin significantly inhibited IRES-mediated translation of Sp1, suggesting that nucleolin positively facilitates Sp1 IRES activation. Further analysis of the interaction between nucleolin and the 5'-UTR of Sp1 mRNA revealed that the GAR domain was important for IRES-mediated translation of Sp1. Moreover, gefitinib, and LY294002 and MK2206 compounds inhibited IRES-mediated Sp1 translation, implying that activation of the epithelial growth factor receptor (EGFR) pathway via Akt activation triggers the IRES pathway. In conclusion, EGFR activation-mediated nucleolin phosphorylated at Thr641 and Thr707 was recruited to the 5'-UTR of Sp1 as an IRES trans-acting factor to modulate Sp1 translation during lung cancer formation.",
keywords = "EGFR, IRES, Nucleolin, Phosphorylation, Sp1",
author = "Hung, {Chia Yang} and Yang, {Wen Bin} and Wang, {Shao An} and Hsu, {Tsung I.} and Chang, {Wen Chang} and Hung, {Jan Jong}",
year = "2014",
month = "8",
day = "27",
doi = "10.1016/j.bbamcr.2014.08.009",
language = "English",
volume = "1843",
pages = "2843--2854",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "12",

}

TY - JOUR

T1 - Nucleolin enhances internal ribosomal entry site (IRES)-mediated translation of Sp1 in tumorigenesis

AU - Hung, Chia Yang

AU - Yang, Wen Bin

AU - Wang, Shao An

AU - Hsu, Tsung I.

AU - Chang, Wen Chang

AU - Hung, Jan Jong

PY - 2014/8/27

Y1 - 2014/8/27

N2 - Our previous study indicated that specificity protein-1 (Sp1) is accumulated during hypoxia in an internal ribosomal entry site (IRES)-dependent manner. Herein, we found that the Sp1 was induced strongly at the protein level, but not in the mRNA level, in lung tumor tissue, indicating that translational regulation might contribute to the Sp1 accumulation during tumorigenesis. A further study showed that the translation of Sp1 was dramatically induced through an IRES-dependent pathway. RNA immunoprecipitation analysis of proteins bound to the 5'-untranslated region (5'-UTR) of Sp1 identified interacting protein - nucleolin. Knockdown of nucleolin significantly inhibited IRES-mediated translation of Sp1, suggesting that nucleolin positively facilitates Sp1 IRES activation. Further analysis of the interaction between nucleolin and the 5'-UTR of Sp1 mRNA revealed that the GAR domain was important for IRES-mediated translation of Sp1. Moreover, gefitinib, and LY294002 and MK2206 compounds inhibited IRES-mediated Sp1 translation, implying that activation of the epithelial growth factor receptor (EGFR) pathway via Akt activation triggers the IRES pathway. In conclusion, EGFR activation-mediated nucleolin phosphorylated at Thr641 and Thr707 was recruited to the 5'-UTR of Sp1 as an IRES trans-acting factor to modulate Sp1 translation during lung cancer formation.

AB - Our previous study indicated that specificity protein-1 (Sp1) is accumulated during hypoxia in an internal ribosomal entry site (IRES)-dependent manner. Herein, we found that the Sp1 was induced strongly at the protein level, but not in the mRNA level, in lung tumor tissue, indicating that translational regulation might contribute to the Sp1 accumulation during tumorigenesis. A further study showed that the translation of Sp1 was dramatically induced through an IRES-dependent pathway. RNA immunoprecipitation analysis of proteins bound to the 5'-untranslated region (5'-UTR) of Sp1 identified interacting protein - nucleolin. Knockdown of nucleolin significantly inhibited IRES-mediated translation of Sp1, suggesting that nucleolin positively facilitates Sp1 IRES activation. Further analysis of the interaction between nucleolin and the 5'-UTR of Sp1 mRNA revealed that the GAR domain was important for IRES-mediated translation of Sp1. Moreover, gefitinib, and LY294002 and MK2206 compounds inhibited IRES-mediated Sp1 translation, implying that activation of the epithelial growth factor receptor (EGFR) pathway via Akt activation triggers the IRES pathway. In conclusion, EGFR activation-mediated nucleolin phosphorylated at Thr641 and Thr707 was recruited to the 5'-UTR of Sp1 as an IRES trans-acting factor to modulate Sp1 translation during lung cancer formation.

KW - EGFR

KW - IRES

KW - Nucleolin

KW - Phosphorylation

KW - Sp1

UR - http://www.scopus.com/inward/record.url?scp=84907462374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907462374&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2014.08.009

DO - 10.1016/j.bbamcr.2014.08.009

M3 - Article

AN - SCOPUS:84907462374

VL - 1843

SP - 2843

EP - 2854

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

SN - 0167-4889

IS - 12

ER -