I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity.
The NF-kappa B transcription factor complex is comprised of two subunits, p50 and p65, that share significant homology to the rel oncogene. We have isolated a cDNA encoding a novel 66-kD rel-related protein, designated I-Rel. Unlike other rel-related proteins, I-Rel does not interact with DNA. I-Rel forms heterodimers with p50, however, and greatly attenuates its DNA-binding activity--an effect probably resulting from the presence of a domain inhibitory to DNA binding present within the 121 amino-terminal residues of I-Rel. In contrast, I-Rel does not associate with p65. Transfection experiments demonstrate that I-Rel suppresses NF-kappa B-induced transcription, probably through its association with p50. Expression of I-Rel mRNA is induced by mitogenic stimulation and accumulates after the appearance of p50 transcripts. Our findings suggest that p50 and I-Rel are components of a feedback pathway where expression of I-Rel may modulate indirectly the expression of genes responsive to the NF-kappa B transcription factor complex.
Ruben
S M
SM
Department of Gene Regulation, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Klement
J F
JF
Coleman
T A
TA
Maher
M
M
Chen
C H
CH
Rosen
C A
CA
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D004247:DNA / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics*; D020572:Oncogene Proteins v-rel; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics
D016328:NF-kappa B; D020572:Oncogene Proteins v-rel; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D051841:Transcription Factor RelB; D004247:DNA; D011505:Protein-Tyrosine Kinases