Opposite role of Ras in tumor necrosis factor-α-induced cell cycle regulation

Competition for Raf kinase

Soo Jung Park, Young Youl Kim, Joong Yeon Lim, Gil Ju Seo, Joon Kim, Sang Ick Park, Bum Joon Park

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Ras, a well-known oncogene, induces cell cycle stimulation through the Raf/Erk pathway and leads to cellular transformation, accompanied by other oncogenes such as c-myc and viral oncogenic protein. Here we suggest the interfering role of Ras in tumor necrosis factor (TNF)-α-induced cell cycle regulation. In TSU-Pr1 and T24 (oncogenic Ras cell lines), TNF-α suppresses cell cycle progression without induction of apoptosis, whereas AGS (wild-type Ras) is stimulated in its cell cycle by TNF-α coupled with activation of Erk. However, in TSU-Pr1 and T24, TNF-α leads to dephosphorylation of Erk1/2. Inhibition or activation of Ras can restore or convert TNF-α-induced cell cycle regulation in the cell lines containing the oncogenic Ras (TSU-Pr1 and T24) or AGS, respectively. Regulation of Erk also shows the coincidental pattern. We suggest the competition between the Ras pathway and TNF signaling for the binding to Raf, a common downstream target, as the cause of such reciprocal response, based on co-immunoprecipitation (co-IP) with antibodies against Raf and Ras or cellular Flice-inhibitory protein (c-FLIP), which have been recently identified upstream of Raf in death-ligand-induced cell cycle stimulation. Overexpression of Raf in TSU-Pr1, to reduce the competition, overcomes TNF-induced cell cycle arrest, also supporting our hypotheses.

Original languageEnglish
Pages (from-to)1140-1147
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume287
Issue number5
DOIs
Publication statusPublished - 2001 Oct 12

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raf Kinases
Cell Cycle
Tumor Necrosis Factor-alpha
Cells
Oncogenes
Cell Line
Chemical activation
Viral Proteins
Cell Cycle Checkpoints
Immunoprecipitation
Apoptosis
Ligands
Proteins
Antibodies

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Opposite role of Ras in tumor necrosis factor-α-induced cell cycle regulation : Competition for Raf kinase. / Park, Soo Jung; Kim, Young Youl; Lim, Joong Yeon; Seo, Gil Ju; Kim, Joon; Park, Sang Ick; Park, Bum Joon.

In: Biochemical and Biophysical Research Communications, Vol. 287, No. 5, 12.10.2001, p. 1140-1147.

Research output: Contribution to journalArticle

Park, Soo Jung ; Kim, Young Youl ; Lim, Joong Yeon ; Seo, Gil Ju ; Kim, Joon ; Park, Sang Ick ; Park, Bum Joon. / Opposite role of Ras in tumor necrosis factor-α-induced cell cycle regulation : Competition for Raf kinase. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 287, No. 5. pp. 1140-1147.
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