Distinct apoptotic responses imparted by c-myc and max

Chadd Nesbit, Saijun Fan, Hong Zhang, Edward V. Prochownik

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The c-myc oncoprotein accelerates programmed cell death (apoptosis) after growth factor deprivation or pharmacological insult in many cell lines. We have shown that max, the obligate c-myc heterodimeric partner protein, also promotes apoptosis after serum withdrawal in NIH3T3 fibroblasts or cytokine deprivation in interleukin-3 (IL-3)-dependent 32D murine myeloid cells. We now show that c-myc- and max-overexpressing 32D cells differ in the nature of their apoptotic responses after IL-3 removal or treatment with chemotherapeutic compounds. In the presence of IL-3, c-myc overexpression enhances the sensitivity of 32D cells to Etoposide (Sigma, St Louis, MO), Adriamycin (Pharmacia, Columbus, OH), and Camptothecin (Sigma), whereas max overexpression increases sensitivity only to Camptothecin. Drug treatment of c-myc-overexpressing cells in the absence of IL-3 did not alter the spectrum of drug sensitivity other than to additively accelerate cell death. In contrast, enhanced sensitivity to Adriamycin, Etoposide, and Taxol (Bristol- Meyers Squibb, Princeton, NJ) was revealed in max-overexpressing cells concurrently deprived of IL-3. Differential rates of apoptosis were not strictly correlated with the ability of the drugs to promote G1 or G2/M arrest. Ectopic expression of Bcl-2 or Bcl-X(L) blocked drug-induced apoptosis in both cell lines. In contrast, whereas Bcl-2 blocked apoptosis in both cell lines in response to IL-3 withdrawal, Bcl-X(L) blocked apoptosis in max-overexpressing cells but not in c-myc-overexpressing cells. These results provide mechanistic underpinnings for the idea that c-myc and max modulate distinct apoptotic pathways.

Original languageEnglish (US)
Pages (from-to)1003-1010
Number of pages8
JournalBlood
Volume92
Issue number3
StatePublished - Aug 1 1998

All Science Journal Classification (ASJC) codes

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

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  • Cite this

    Nesbit, C., Fan, S., Zhang, H., & Prochownik, E. V. (1998). Distinct apoptotic responses imparted by c-myc and max. Blood, 92(3), 1003-1010.