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

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. P...

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Main Authors: Hjelmsoe, I, Cohn, M, Tulchinsky, E, Allen, C, Wu, L
Format: Journal article
Published: 2000
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author Hjelmsoe, I
Cohn, M
Tulchinsky, E
Allen, C
Wu, L
author_facet Hjelmsoe, I
Cohn, M
Tulchinsky, E
Allen, C
Wu, L
author_sort Hjelmsoe, I
collection OXFORD
description 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.
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spelling oxford-uuid:8b0131f9-5d56-4974-9193-e887fb29a0152022-03-26T22:35:18ZThe κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8b0131f9-5d56-4974-9193-e887fb29a015Symplectic Elements at Oxford2000Hjelmsoe, ICohn, MTulchinsky, EAllen, CWu, LA 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.
spellingShingle Hjelmsoe, I
Cohn, M
Tulchinsky, E
Allen, C
Wu, L
The κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1
title The κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1
title_full The κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1
title_fullStr The κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1
title_full_unstemmed The κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1
title_short The κB and V(D)J recombination signal sequence binding protein KRC regulates transcription of the mouse metastasis-associated gene S100A4/mts1
title_sort κb and v d j recombination signal sequence binding protein krc regulates transcription of the mouse metastasis associated gene s100a4 mts1
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