Mxi1-0, an alternatively transcribed Mxi1 isoform, is overexpressed in glioblastomas.

Published

Journal Article

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.

Full Text

Cited Authors

  • Engstrom, LD; Youkilis, AS; Gorelick, JL; Zheng, D; Ackley, V; Petroff, CA; Benson, LQ; Coon, MR; Zhu, X; Hanash, SM; Wechsler, DS

Published Date

  • September 2004

Published In

Volume / Issue

  • 6 / 5

Start / End Page

  • 660 - 673

PubMed ID

  • 15548375

Pubmed Central ID

  • 15548375

Electronic International Standard Serial Number (EISSN)

  • 1476-5586

International Standard Serial Number (ISSN)

  • 1522-8002

Digital Object Identifier (DOI)

  • 10.1593/neo.04244

Language

  • eng