The DNA binding subunit of NF-κB is identical to factor KBF1 and homologous to the rel oncogene product

Kieran, Mark W.; Blank, Volker; Logeat, Frédérique; Vandekerckhove, Joël; Lottspeich, F.; Bail, O Le; Urban, Manuela; Kourilsky, Philippe; Baeuerle, Patrick A.; Israël, Alain

doi:10.1016/0092-8674(90)90275-j

Cited by 878 publications

(672 citation statements)

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“…REV-T originated by the transduction of a turkey c-rel gene by a Reticuloendotheliosis associated virus (REV-A) (Breitman et al, 1980;Hoelzer et al, 1979;Wilhelmsen et al, 1984). c-Rel is a member of the Rel/NF-kB family of transcription factors (Gilmore, 1990;Kieran et al, 1990).…”

mentioning

confidence: 99%

“…v-Rel is able to bind kB sites and the principal region that provides v-Rel with this ability is the RHR (Kabrun et al, 1991;Kieran et al, 1990;Kochel and Rice, 1992;Morrison et al, 1992;Sarkar and Gilmore, 1993). Crystallographic analysis performed on p50 (NF-kB1) demonstrated that the RHR consits of two barrel-like domains (Ghosh et al, 1995;MuÈ ller et al, 1995) (see Figure 1a).…”

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confidence: 99%

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Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein

1997

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The oncogene v-rel of Reticuloendotheliosis virus, strain T, is derived from an avian c-rel proto-oncogene. c-rel encodes a member of the Rel/NF-kB family of transcription factors. The highly oncogenic v-Rel di ers from c-Rel which has low transforming potential by the acquisition of numerous mutations. In this manuscript, we demonstrate that the oncogenic mutations in v-Rel directly alter the ability of this protein to bind to DNA. Electrophoretic mobility shift analysis with Rel proteins synthesized in vitro as well as isolated from nuclei of Rel expressing cells showed that three mutation clusters, present in the N-terminus, the center and the C-terminus of v-Rel, altered three di erent aspects of DNA binding. In contrast, the oncogenic C-terminal deletion of 118 amino acids present in v-Rel had almost no in¯uence on its DNA binding. The N-terminal mutation cluster altered the kB DNA-binding speci®city of the v-Rel oncoprotein relative to c-Rel. The mutation Met-20?Thr was found to be principally responsible for this alteration. The second mutation cluster was responsible for increased binding of v-Rel to all the kB sites examined presumably because it stabilized v-Rel homodimers. This alteration in DNA binding was mapped to the group of two mutations within the cluster. In contrast, the third mutation cluster in the C-terminus of v-Rel destabilized the binding of v-Rel to all of the kB sites examined. This is the ®rst indication that regions outside the Rel Homology Region can participate in the control of binding of the c-Rel protein to DNA. The three mutation clusters examined contributed to the tumorigenic potential of v-Rel with the relative strength decreasing with their position from the N-terminus to the C-terminus. These results suggest that the oncogenic mutations in v-Rel cooperate and enable v-Rel to form nuclear complexes with aberrant DNA-binding properties that may directly alter gene expression and DNA replication resulting in the transformation of the cell.

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confidence: 99%

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confidence: 99%

Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein

1997

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“…If dorsal protein were maintained in the cytoplasm (56) by associations with actin filaments, then reorganizations of these filaments could release it, permitting it to be transported into the nucleus. In support of this speculation is a recent report of the sequence of a dorsal-related protein, KBF1, which contains in its carboxy terminus a sequence reminiscent of the repeats in a spectrin-binding protein, ankyrin (57) .…”

Section: Actin and The Specification Of The Dorsal-ventral Axismentioning

confidence: 92%

Actin in the Drosophila embryo: Is there a relationship to developmental cue localization?

Bearer¹

1991

BioEssays

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SummaryRecent genetic manipulations have revealed that the cytoplasm of the early Drosophila embryo contains localized information that specifies the future embryonic axes. It is the restricted distribution or activity of particular gene products, either messenger RNA or protein, that is crucial for this specification. While some of the genes responsible for this information have been sequenced and the nature and distribution of their products examined, it is not known how this localization is established or maintained. The actin-based cytoskeleton is a likely candidate for the formation, of a cytomatrix that would allow such distributions and yet no direct evidence has yet been found that implicates actin in positional cue localization. In this review I summarize what is known about actin filament behavior in Drosophila embryos and compare it to the distribution of positional cues. My purpose is to juxtapose these two bodies of information such that the relationship between them may be revealed.

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“…Cloning of the cDNAs encoding NF-kB p50 and p65 subunits revealed that both proteins are homologous to the product of the c-rel proto-oncogene. The homology that exists among p50, p65 and c-Rel is observed within an approximately 300 amino acid region, the Rel homology domain, which is common to all NF-kB family members (Kieran et al, 1990;Ruben et al, 1991). This essential region is multifunctional, controlling NF-kB dimerization, interaction with IkB, DNAbinding and it also contains the nuclear localization signal.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of NF-κB activity and NF-κB p65 subunit expression by ras and polyoma middle T oncogenes in human colonic Caco-2 cells

et al. 1997

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The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21 ras or pp60 c-src in human colonic cells is associated with alterations of the activity and expression of nuclear factor kB (NF-kB), a transcription factor suspected to participate in the development of cancer. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated Val-12 human Ha-ras gene or with the polyoma middle T (PyMT) oncogene, a constitutive activator of pp60 c-src tyrosine kinase activity. Compared with control vectortransfected Caco-2 cells, both oncogene-transfected cell lines exhibited: (i) decreased constitutive NF-kB DNAbinding activity and NF-kB-mediated reporter gene expression, without alteration of their response to TNF-a for activation of these parameters; (ii) reduced NF-kB cytosolic stores along with a decreased p65 expression due, at least in part, to destabilization of p65 mRNA; (iii) a decrease in adhesion to extracellular matrix component-coated substrata which was partially corrected when stimulating NF-kB transcriptional activity with TNF-a. These results indicate that the tumorigenic progression induced by oncogenic p21 ras or PyMT/pp60 c-src in human colonic Caco-2 cells is associated with a down-regulation of p65 expression and NF-kB activity which could be responsible for the reduced adhesive properties of these cells after oncogene transfection.

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The DNA binding subunit of NF-κB is identical to factor KBF1 and homologous to the rel oncogene product

Cited by 878 publications

References 43 publications

Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein

Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein

Actin in the Drosophila embryo: Is there a relationship to developmental cue localization?

Down-regulation of NF-κB activity and NF-κB p65 subunit expression by ras and polyoma middle T oncogenes in human colonic Caco-2 cells

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