Abstract
dMax, a naturally occurring splice variant of the Myc binding protein Max, lacks the DNA binding basic region and helix 1 of the Helix – Loop – Helix domain; dMax interacts with c-Myc in vitro and in vivo, and inhibits E-box Myc site driven transcription in transient transfection assays. Here we have investigated the expression, function and interactions of dMax. RT/PCR analyses detected dmax mRNA in multiple tissues of the developing, newborn and adult mouse. Functionally, dMax reduced the ability of c-Myc to cooperate with the progression factor A-Myb to promote S phase entry of quiescent smooth muscle cells. In contrast, dMax failed to ablate inhibition of initiator element (Inr)-mediated transcription by c-Myc in Jurkat T cells. In in vitro protein : protein association assays, dMax interacted with c-Myc, N-Myc, L-Myc, Mad1, Mxi1, Mad3 and Mad4, but not with itself or wild-type Max. These interactions required an intact leucine zipper. Inhibition of E-box-mediated transactivation by induction of dMax overexpression resulted in apoptosis of WEHI 231 B cells. Thus, dMax is a widely expressed, naturally occurring protein, with the capacity to bind most members of the Myc/Max superfamily; dMax has little effect on Inr-mediated repression by c-Myc, but can significantly decrease E-box-mediated events promoting proliferation and cell survival.
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Acknowledgements
We express our gratitude to Stephen Hann for providing Max antibodies and plasmid constructs, as well as Fred Alt, Robert Eisenman, Ed Prochownik, Ananda Roy and Daniel Wechsler for other plasmid constructs used in this study. We also thank David Sherr for helpful comments and critical reading of the manuscript. This work was supported by NIH grants T32-CA64070 (MJF) and CA36355 (GES) and a grant from the Cure for Lymphoma Foundation (MA).
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FitzGerald, M., Arsura, M., Bellas, R. et al. Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc. Oncogene 18, 2489–2498 (1999). https://doi.org/10.1038/sj.onc.1202611
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DOI: https://doi.org/10.1038/sj.onc.1202611
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