Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc
| Autor: | Min Wu, Robert E. Bellas, Koren K. Mann, William Yang, M J FitzGerald, Gail E. Sonenshein, Marcello Arsura, Lynda Chin, Ronald A. DePinho |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Leucine zipper Transcription Genetic Genes myc E-box Apoptosis Biology Regulatory Sequences Nucleic Acid Jurkat cells Muscle Smooth Vascular Transactivation Mice Initiator element Transcription (biology) Gene expression Genetics Animals Protein Splicing Molecular Biology Transcription factor B-Lymphocytes Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Helix-Loop-Helix Motifs Gene Expression Regulation Developmental Molecular biology DNA-Binding Proteins Basic-Leucine Zipper Transcription Factors Cell Division Transcription Factors |
| Zdroj: | Oncogene. 18(15) |
| ISSN: | 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|