The κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1

Iben Hjelmsoe, Carl E. Allen, Martin A. Cohn, Eugene M. Tulchinsky, Lai Chu Wu

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

A κB-like sequence, Sb, is integral to the composite enhancer located in the first intron of the metastasis-associated gene, S100A4/mts1. Oligonucleotides containing this sequence form three specific complexes with nuclear proteins prepared from S100A4/mts1-expressing CSML100 adenocarcinoma cells. Protein studies show the Sb-interacting complexes include NF-κB/Rel proteins, p50·p50 and p50·p65 dimers. Additionally, the Sb sequence was bound by an unrelated ~200-kDa protein, p200. Site-directed mutagenesis in conjunction with transient transfections indicate that p200, but not the NF- κB/Rel proteins, transactivates S100A4/mts1. To identify candidate genes for p200, double-stranded DNA probes containing multiple copies of Sb were used to screen a randomly primed λgt11 cDNA expression library made from CSML100 poly(A)+ RNA. Two clones corresponding to the DNA-binding proteins KRC and Alf1 were identified. KRC encodes a large zinc finger protein that binds to the κB motif and to the signal sequences of V(D)J recombination. In vitro DNA binding assays using bacterially expressed KRC fusion proteins, demonstrate specific binding of KRC to the Sb sequence. In addition, introduction of KRC expression vectors into mammalian cells induces expression of S100A4/mts1 and reporter genes driven by S100A4/mts1 gene regulatory sequences. These data indicate that KRC positively regulates transcription of S100A4/mts1.

Original languageEnglish
Pages (from-to)913-920
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number2
DOIs
Publication statusPublished - Jan 14 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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