Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The v-rel oncogene product from the avian reticuloendotheliosis virus strain T corresponds to a member of the Rel-related family of enhancer-binding proteins that includes both the mammalian 50- and 65-kDa subunits of the NF-kappa B transcription factor complex. However, in contrast to NF-kappa B, v-Rel has been shown to function as a dominant-negative repressor of kappa B-dependent transcription in many mature cell types. We now demonstrate that a highly conserved motif within the Rel homology domain of v-Rel containing a consensus protein kinase A phosphorylation site is required for DNA binding, transcriptional repression, and cellular transformation mediated by this oncoprotein. However, replacement of the serine phosphate acceptor within the protein kinase A site with an alanine did not alter any of these functions of v-Rel, suggesting that phosphorylation at this site is not central to the regulation of this oncogene product. Rather, the inactive mutations appear to identify a functional domain within v-Rel required for these various biological activities. It is notable that these same mutations do not impair the ability of v-Rel to heterodimerize with the 50-kDa subunit of NF-kappa B, suggesting that v-Rel-mediated transcriptional repression likely involves direct nuclear blockade of the kappa B enhancer rather than indirect alterations in the composition of preformed cytoplasmic NF-kappa B complexes. Paradoxically, when introduced into undifferentiated F9 cells, v-Rel functions as a kappa B-specific transcriptional activator rather than as a dominant-negative repressor. These stimulatory effects of v-Rel require both the conserved protein kinase A phosphorylation site and additional unique C-terminal sequences not needed for v-Rel-mediated repression in mature cells. Retinoic acid-induced differentiation of these F9 cells restores the repressor function of v-Rel. These opposing biological actions of v-Rel occurring in cells at distinct stages of differentiation may have important implications for the mechanism of v-Rel-mediated transformation occurring in avian splenocytes.
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PMID:The v-rel oncogene: insights into the mechanism of transcriptional activation, repression, and transformation. 132 Dec 84

HIVEN86A is an inducible member of a set of cellular proteins that specifically bind to the kappa B enhancer (Franza et al., 1987; Franza, 1988; Franza, 1990; Ballard et al., 1989; Bohnlein et al., 1988). This enhancer motif has been detected in numerous cellular and viral transcription control domains (Boshart et al., 1985; Sen & Baltimore, 1986; Nabel & Baltimore, 1987). Recently, cDNAs have been cloned (Kieran et al., 1990; Baldwin & Sharp, 1987) that encode the 50 kD DNA binding subunit of murine NF-kappa B (for review: Leonardo & Baltimore, 1989) and the closely related human kappa binding factor (KBF-1) (Kimura et al., 1986; Baldwin & Sharp, 1987). A 350 amino acid domain at the N-terminus of these proteins was found to be homologous with the v-rel oncogene from the avian reticuloendotheliosis virus, strain T (REV-T), as well as a maternal effect gene, dorsal (Kieran et al., 1990; Ghosh et al., 1990). Dorsal is known to activate transcription of certain Drosophila genes (Rushlow et al., 1987). The v-Rel oncoprotein has been identified as a transcriptional activator (Gelinas & Temin, 1988; Hannink & Temin, 1989; Bull et al., 1990) in certain assay systems and shown to be induced by the tumor promoter, phorbol 12-myristate 13-acetate (PMA) in avian cells (for review: Rice & Gilden, 1988). HIVEN86A is also inducible by PMA (Franza et al., 1987; Franza, 1988; Franza, 1990). We now demonstrate that the protein product of the human c-rel proto-oncogene is structurally identical to HIVEN86A.
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PMID:A member of the set of kappa B binding proteins, HIVEN86A, is a product of the human c-rel proto-oncogene. 203 Sep 15