Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc.
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.
FitzGerald
M J
MJ
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Arsura
M
M
Bellas
R E
RE
Yang
W
W
Wu
M
M
Chin
L
L
Mann
K K
KK
DePinho
R A
RA
Sonenshein
G E
GE
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D016259:Genes, myc; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019154:Protein Splicing; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors; D014158:Transcription, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D014157:Transcription Factors; C068422:Max protein, mouse