Isolation of a
            <i>rel</i>
            -related Human cDNAThat Potentially Encodes the 65-kD Subunit of NF-κB

Ruben, Steven M.; Dillon, Patrick; Schreck, Ralf; Henkel, Thomas; Chen, Chein-Hwa; Maher, Maureen; Baeuerle, Patrick A.; Rosen, Craig A.

doi:10.1126/science.2006423

Cited by 434 publications

(221 citation statements)

References 27 publications

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“…This region is also found in the products of the proto-oncogene c-rel and of the dorsal maternal effect gene of Drosophila melanogaster (16,31,32,38,80). The Rel homology region of these proteins mediates DNA binding, dimerization, nuclear targeting, and interactions with IKB (9,11,17,31,33,45,63,72). …”

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confidence: 99%

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Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.

Stein¹,

Cogswell²,

Baldwin³

1993

Mol. Cell. Biol.

498

340

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NF-KB and C/EBP represent distinct families of transcription factors that target unique DNA enhancer elements. The heterodimeric NF-KB complex is composed of two subunits, a 50-and a 65-kDa protein. All members of the NF-cB family, including the product of the proto-oncogene c-rel, are characterized by their highly homologous -300-amino-acid N-terminal region. This Rel homology domain mediates DNA binding, dimerization, and nuclear targeting of these proteins. C/EBP contains the bZIP region, which is characterized by two motifs in the C-terminal half of the protein: a basic region involved in DNA binding and a leucine zipper motif involved in dimerization. The C/EBP family consists of several related proteins, C/EBPa, C/EBP3, C/EBP-y, and C/EBP8, that form homodimers and that form heterodimers with each other. We now demonstrate the unexpected cross-coupling of members of the NF-cB family with three members of the C/EBP family. NF-cB p65, p50, and Rel functionally synergize with C/EBPa, C/EBPf3, and C/EBP8. This cross-coupling results in the inhibition of promoters with KB enhancer motifs and in the synergistic stimulation of promoters with C/EBP binding sites. These studies demonstrate that NF-KB augments gene expression mediated by a multimerized c-fos serum response element in the presence of C/EBP. We show a direct physical association of the bZIP region of C/EBP with the Rel homology domain of NF-KB. The cross-coupling of NF-cB with C/EBP highlights a mechanism of gene regulation involving an interaction between distinct transcription factor families.Transcriptional regulation of gene expression is controlled by factors that bind to specific DNA sequences. Many of these factors can be classified into distinct families based on common structural motifs. These families include the homeodomain family (30), the zinc finger proteins (26, 46), the leucine zipper family (49,84), and the helix-loop-helix family (59, 60). Many of these transcription factors bind to their cognate DNA motifs as homodimers and, moreover, there are multiple examples of heterodimer formation within the same family of transcription factors. However, there is growing evidence that these dimerization motifs are also involved in interactions between transcription factors from different families. Examples are the interaction of the Jun leucine zipper region with the helix-loop-helix motif of MyoD (12) (24,42,74,87). This cross-coupling between different families might lead to the formation of novel transcription factor complexes displaying altered biological activities.The transcription factor NF-KB binds to KB enhancer motifs found in a variety of genes in response to various signals (5 and references therein, 35, 51). NF-KB DNA binding activity typically involves two subunits, a 50-kDa protein (17, 31, 45) and a 65-kDa protein (63,72). NF-KB p50 and NF-KB p65 share a highly homologous 300-residue N-terminal region. This region is also found in the products of the proto-oncogene c-rel and of the dorsal maternal effect gene of Drosophila mela...

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confidence: 99%

“…NF-KB DNA binding activity typically involves two subunits, a 50-kDa protein (17, 31, 45) and a 65-kDa protein (63,72). NF-KB p50 and NF-KB p65 share a highly homologous 300-residue N-terminal region.…”

mentioning

confidence: 99%

Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.

Stein¹,

Cogswell²,

Baldwin³

1993

Mol. Cell. Biol.

498

340

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“…The ReIA(p65) and RelB subunits are most highly homologous to c-Rel (49,58,59,61) and contain transactivation domains in their carboxy termini (12,27,31,49,55,60,61,63). Two related cDNAs encoding the larger precursor proteins of the 50-kDa DNAbinding subunits of NF-KB, NF-KB1(p105) (10,22,34,44) and NF-KB2(plOO) (9,47,62), have been isolated.…”

mentioning

confidence: 99%

An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation.

Perkins¹,

Agranoff²,

Pascal³

et al. 1994

Mol. Cell. Biol.

225

157

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Induction of human immunodeficiency virus type 1 (HIV-1) gene expression in stimulated T cells has been attributed to the activation of the transcription factor NF-KB. The twice-repeated KB sites within the HIV-1 long terminal repeat are in close proximity to three binding sites for Spl. We have previously shown that a cooperative interaction of NF-KB with Spl is required for the efficient stimulation of HIV-1 transcription. In this report, we define the domains of each protein responsible for this effect. Although the transactivation domains seemed likely to mediate this interaction, we find, surprisingly, that this interaction occurs through the putative DNA-binding domains of both proteins. Spl specifically interacted with the amino-terminal region of ReIA(p65). Similarly, RelA bound directly to the zinc finger region of Spl. This interaction was specific and resulted in cooperative DNA binding to the icB and Spl sites in the HIV-1 long terminal repeat. Furthermore, the amino-terminal region of RelA did not associate with several other transcription factors, including MyoD, E12, or Koxl5, another zinc finger protein. These findings suggest that the juxtaposition of DNA-binding sites promotes a specific protein interaction between the DNA-binding regions of these transcription factors. This interaction is required for HIV transcriptional activation and may provide a mechanism to allow for selective activation of KB-regulated genes.

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“…15 The NF-B transcription factor family consists of five different members, called p50, p52, p65 (RelA), c-Rel, and RelB, which can form various homo-and heterodimers. 16,17 The active forms of NF-B are heterodimers composed most often of p50 and p65. There are two main isoforms of I B in mammalian cells that have been extensively characterized, I B-␣ and I B-␤.…”

mentioning

confidence: 99%

Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor ?B independently of I?B degradation

et al. 1998

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Isolation of a rel -related Human cDNAThat Potentially Encodes the 65-kD Subunit of NF-κB

Cited by 434 publications

References 27 publications

Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.

Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.

An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation.

Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor ?B independently of I?B degradation

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