Effect of cell cycle on the regulation of the cell surface and secreted forms of type I and type II human tumor necrosis factor receptors

Eva Pocsik, Rudolf Mihalik, Maria Penzes, Hansruedi Loetscher, Harald Gallati, Bharat B. Aggarwal

Research output: Article

12 Citations (Scopus)


The cell cycle has been shown to regulate the biological effects of human tumor necrosis factor (TNF), but to what extent that regulation is due to the modulation of TNF receptors is not clear. In the present report we investigated the effect of the cell cycle on the expression of surface and soluble TNF receptors in human histiocytic lymphoma U‐937. Exposure to hydroxyurea, thymidine, etoposide, bisbensimide, and democolcine lead to accumulation of cells primarily in G1/S, S, S/G2/M, G2/M, and M stages of the cell cycle, respectively. Whilie no significant change in TNF receptors occurred in cells arrested in G1/S or S/G2 stages, about a 50% decrease was observed in cells at M phase of the cycle. Scatchard analysis showed a reduction in receptor number rather than affinity. In contrast, cells arrested at S phase (thymidine) showed an 80% increase in receptor number. The decrease in the TNF receptors was not due to changes in cell size or protein synthesis. The increase in receptors, however, correlated with an increase in total protein synthesis (to 3.8‐fold of the control levels). A proportional change was observed in the p60 and p80 forms of the TNF receptors. A decrease in the surface receptors in cells arrested in M phase correlated with an increase in the amount of soluble receptors. The cellular response to TNF increased to 8‐ and 2‐fold in cells arrested in G1 and S phase, respectively; but cells at G2/M phase showed about 6‐fold decrease in response. In conclusion, our results demonstrate that the cell cycle plays an important role in regulation of cell‐surface and soluble TNF receptors and also in the modulation of cellular response. © 1995 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)303-316
Number of pages14
JournalJournal of cellular biochemistry
Issue number3
Publication statusPublished - nov. 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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