Mxi1-0, an alternatively transcribed Mxi1 isoform, is overexpressed in glioblastomas.
The c-Myc transcription factor regulates expression of genes related to cell growth, division, and apoptosis. Mxi1, a member of the Mad family, represses transcription of c-Myc-regulated genes by mediating chromatin condensation via histone deacetylase and the Sin3 corepressor. Mxi1 is a c-Myc antagonist and suppresses cell proliferation in vitro. Here, ... we describe the identification of Mxi1-0, a novel Mxi1 isoform that is alternatively transcribed from an upstream exon. Mxi1-0 and Mxi1 have different amino-terminal sequences, but share identical Max- and DNA-binding domains. Both isoforms are able to bind Max, to recognize E-box binding sites, and to interact with Sin3. Despite these similarities and in contrast to Mxi1, Mxi1-0 is predominantly localized to the cytoplasm and fails to repress c-Myc-dependent transcription. Although Mxi1-0 and Mxi1 are coexpressed in both human and mouse cells, the relative levels of Mxi1-0 are higher in primary glioblastoma tumors than in normal brain tissue. This variation in the levels of Mxi1-0 and Mxi1 suggests that Mxi1-0 may modulate the Myc-inhibitory activity of Mxi1. The identification of Mxi1-0 as an alternatively transcribed Mxi1 isoform has significant implications for the interpretation of previous Mxi1 studies, particularly those related to the phenotype of the mxi1 knockout mouse.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Basic-Leucine Zipper Transcription Factors, COS Cells, Cercopithecus aethiops, Chromosomes, Human, Pair 10, Cytoplasm, DNA-Binding Proteins, Exons, Gene Expression Regulation, Neoplastic, Glioblastoma, Humans, Mice, Molecular Sequence Data, Neuroblastoma, Promoter Regions, Genetic, Protein Isoforms, RNA, Messenger, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins, Up-Regulation
Amino Acid Sequence, Animals, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Basic-Leucine Zipper Transcription Factors, COS Cells, Cercopithecus aethiops, Chromosomes, Human, Pair 10, Cytoplasm, DNA-Binding Proteins, Exons, Gene Expression Regulation, Neoplastic, Glioblastoma, Humans, Mice, Molecular Sequence Data, Neuroblastoma, Promoter Regions, Genetic, Protein Isoforms, RNA, Messenger, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins, Up-Regulation
Neoplasia
Date: Nov. 19, 2004
PubMed ID: 15548375
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