Induction of apoptosis by the c-Myc helix-loop-helix/leucine zipper domain in mouse 3T3-L1 fibroblasts - PubMed

Affiliations

• PMID: 7499403
• DOI: 10.1074/jbc.270.48.28797

Free article

Induction of apoptosis by the c-Myc helix-loop-helix/leucine zipper domain in mouse 3T3-L1 fibroblasts

F Kohlhuber et al. J Biol Chem. 1995.

Free article

Abstract

The cellular proto-oncogene c-myc is involved in cell proliferation and transformation but is also implicated in the induction of programmed cell death (apoptosis). The c-Myc protein is a transcriptional activator with a carboxyl-terminal basic region/helix-loop-helix (HLH)/leucine zipper (LZ) domain. It forms heterodimers with the HLH/LZ protein Max and transactivates gene expression after binding DNA E-box elements. We have studied the phenotype of dominant-negative mutants of c-Myc and Max in microinjection experiments. Max mutants with a deleted or mutated basic region inhibited DNA synthesis in serum-stimulated 3T3-L1 mouse fibroblasts. In contrast, mutants of c-Myc expressing only the basic region/HLH/LZ or HLH/LZ domains rapidly induced apoptosis at low and high serum levels. Co-expression of the HLH/LZ domains of c-Myc and Max failed to do so. We suggest that the c-Myc HLH/LZ domain induces apoptosis by specific interaction with cellular factors different to Max.

Similar articles

• Analysis of the Myc and Max interaction specificity with lambda repressor-HLH domain fusions.

  Marchetti A, Abril-Marti M, Illi B, Cesareni G, Nasi S. Marchetti A, et al. J Mol Biol. 1995 May 5;248(3):541-50. doi: 10.1006/jmbi.1995.0241. J Mol Biol. 1995. PMID: 7752223

• New structural determinants for c-Myc specific heterodimerization with Max and development of a novel homodimeric c-Myc b-HLH-LZ.

  Beaulieu ME, McDuff FO, Frappier V, Montagne M, Naud JF, Lavigne P. Beaulieu ME, et al. J Mol Recognit. 2012 Jul;25(7):414-26. doi: 10.1002/jmr.2203. J Mol Recognit. 2012. PMID: 22733550

• The basic region/helix-loop-helix/leucine zipper domain of Myc proto-oncoproteins: function and regulation.

  Lüscher B, Larsson LG. Lüscher B, et al. Oncogene. 1999 May 13;18(19):2955-66. doi: 10.1038/sj.onc.1202750. Oncogene. 1999. PMID: 10378692 Review.

• The mycN/max protein complex in neuroblastoma. Short review.

  Wenzel A, Schwab M. Wenzel A, et al. Eur J Cancer. 1995;31A(4):516-9. doi: 10.1016/0959-8049(95)00060-v. Eur J Cancer. 1995. PMID: 7576956 Review.

Cited by

• Intracellular and extracellular leukemia inhibitory factor proteins have different cellular activities that are mediated by distinct protein motifs.

  Haines BP, Voyle RB, Rathjen PD. Haines BP, et al. Mol Biol Cell. 2000 Apr;11(4):1369-83. doi: 10.1091/mbc.11.4.1369. Mol Biol Cell. 2000. PMID: 10749936 Free PMC article.

• Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation.

  Duangmano S, Sae-Lim P, Suksamrarn A, Domann FE, Patmasiriwat P. Duangmano S, et al. BMC Complement Altern Med. 2012 Oct 12;12:185. doi: 10.1186/1472-6882-12-185. BMC Complement Altern Med. 2012. PMID: 23062075 Free PMC article.

• Diminished energy metabolism and enhanced apoptosis in livers of B6C3F1 mice treated with the antihepatocarcinogen rotenone.

  Wang C, Youssef J, Saran B, Rothberg PG, Cunningham ML, Molteni A, Badr M. Wang C, et al. Mol Cell Biochem. 1999 Nov;201(1-2):25-32. doi: 10.1023/a:1007024905046. Mol Cell Biochem. 1999. PMID: 10630619

• Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis.

  Xiao Q, Claassen G, Shi J, Adachi S, Sedivy J, Hann SR. Xiao Q, et al. Genes Dev. 1998 Dec 15;12(24):3803-8. doi: 10.1101/gad.12.24.3803. Genes Dev. 1998. PMID: 9869633 Free PMC article.

Publication types

MeSH terms

Substances