Differential effects of the widely expressed dMax splice variant of Max onE-box vs initiator element-mediated regulation by c-Myc

dMax, a naturally occurring splice variant of the Myc binding protein Mas, lacks the DNA binding basic region and helix 1 of the Helix-Loop-Helix doma in; dMax interacts with c-Myc in vitro and in vivo, and inhibits E-bos Myc site driven transcription in transient transfection assays, Here we have in vestigated the expression, function and interactions of dMax, RT/PCR analys es detected dmax mRNA in multiple tissues of the developing, newborn and ad ult mouse. Functionally, dMax reduced the ability of c-Myc to cooperate,vit h the progression factor A-Myb to promote S phase entry of quiescent smooth muscle cells. In contrast, dMax failed to ablate inhibition of initiator e lement (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-M yc, Mad1, Mxi1, Mad3 and Mad4, but not,vith itself or wild-type Max, These interactions required an intact leucine zipper. Inhibition of E-box-mediate d 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 signi ficantly decrease E-bos-mediated events promoting proliferation and cell su rvival.