Mxi1 isoforms are expressed in hematological cell lines and normal bone marrow.

Abstract:

:Mxi1 protein is a basic helix-loop-helix, leucine zipper (bHLHZIP) transcriptional factor, which dimerizes with the Max protein. This heterodimer binds a specific DNA sequence (E-box) and suppresses transcription of target genes. On the other hand, c-Myc protein is also a bHLHZIP protein that dimerizes with Max, binds the identical E-box sequence but activates transcription of the target genes. We report that hematopoietic cells have three novel Mxi1 transcripts: Mxi-D lacks exon 3, which encodes the basic region; Mxi-ND lacks the N-terminal mSin3 binding region and the DNA binding region; and Mxi-NF lacks the N-terminal mSin3 binding region. In normal bone marrow and hematological cell lines, the dominantly expressed isoforms are Mxi-D and full-length Mxi1 (Mxi-F). In GST-pull down assays, the Mxi-D protein binds the Max protein and the PHA2 regions of mSin3 proteins. Whereas the Mxi-F/Max heterodimer binds the E-box sequence, Mxi-D/Max heterodimer can not bind this sequence in electrophoretic mobility shift assays. In reporter gene assay, Mxi-D suppresses transcription as strongly as Mxi-F. In colony formation assay using Rat1 fibroblast cells, Mxi-D cannot suppress clonal growth stimulated by c-Myc as strongly as Mxi-F. In summary, Mxi-D may play an important role in the c-Myc family protein network acting as a dominant negative isoform of Mxi-F since: i) Mxi-D can dimerize with Max in vitro; ii) Mxi-D/Max heterodimers cannot bind E-box in vitro, iii) Mxi-D cannot suppress clonal growth stimulated by c-Myc.

journal_name

Int J Oncol

authors

Kawamata N,Sugimoto KJ,Sakajiri S,Oshimi K,Koeffler HP

keywords:

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

1369-75

issue

5

eissn

1019-6439

issn

1791-2423

journal_volume

26

pub_type

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