I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity.
We have isolated a human cDNA which encodes a novel I kappa B family member using a yeast two-hybrid screen for proteins able to interact with the p52 subunit of the transcription factor NF-kappa B. The protein is found in many cell types and its expression is up-regulated following NF-kappa B activation and during myelopoiesis. Consistent with its proposed role as an I kappa B molecule, I kappa B-epsilon is able to inhibit NF-kappa B-directed transactivation via cytoplasmic retention of rel proteins. I kappa B-epsilon translation initiates from an internal ATG codon to give rise to a protein of 45 kDa, which exists as multiple phosphorylated isoforms in resting cells. Unlike the other inhibitors, it is found almost exclusively in complexes containing RelA and/or cRel. Upon activation, I kappa B-epsilon protein is degraded with slow kinetics by a proteasome-dependent mechanism. Similarly to I kappa B-alpha and I kappa B, I kappa B-epsilon contains multiple ankyrin repeats and two conserved serines which are necessary for signal-induced degradation of the molecule. A unique lysine residue located N-terminal of the serines appears to be not strictly required for degradation. Unlike I kappa B- alpha and I kappa B-beta, I kappa B-epsilon does not contain a C-terminal PEST-like sequence. I kappa B-epsilon would, therefore, appear to regulate a late, transient activation of a subset of genes, regulated by RelA/cRel NF-kappa B complexes, distinct from those regulated by other I kappa B proteins.
Whiteside
S T
ST
Unité de Biologie Moléculaire de l'Expression Génique, UMR 0321 CNRSInstitut Pasteur, Paris, France.
Epinat
J C
JC
Rice
N R
NR
Israël
A
A
D000595:Amino Acid Sequence; D018076:DNA, Complementary / Q000235:genetics; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors; D015533:Transcriptional Activation
D018076:DNA, Complementary; D020672:I-kappa B Proteins; D016328:NF-kappa B; C105627:NFKBIE protein, human; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; C497593:RELB protein, human; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051841:Transcription Factor RelB