The p50 subunit of NF-kappa B is derived from the amino terminus of a 105 
kilodalton precursor. The p105 carboxyl terminus, which contains ankyrin-like 
repeats, a feature of I kappa B molecules, regulates the cytoplasmic retention 
of p105 and inhibits DNA binding by the precursor. Here, we describe an I kappa 
B protein identical to the carboxyl-terminal region of p105. Probes spanning the 
COOH terminus but not the rel homology domain of p105 hybridize to a distinct 
2.6-kilobase mRNA expressed in a wide range of murine tissues. The nucleotide 
sequence of complementary DNA clones for this transcript, in vitro translation, 
and immune precipitation of metabolically labeled cell lysates establish that it 
encodes a 70 kilodalton protein that corresponds to the COOH-terminal 607 amino 
acids of p105. p70 suppresses p65 and p75c-rel mediated transactivation of 
reporter genes under the control of NF-kappa B elements and in vitro can prevent 
DNA binding of p50 and p75c-rel homodimers to NF-kappa B sites. The ability of 
p70 to stably associate with p49 and p65 in vitro, but not inhibit DNA binding 
by these proteins, suggests that the specific inhibitory properties of this I 
kappa B may reflect its relative affinity for different rel targets. p70 
phosphorylated by protein kinase A fails to inhibit DNA binding by p50 or the 
c-rel protein, and sequencing of radiolabeled p70 tryptic phosphopeptides 
establishes that protein kinase A phosphorylates serine residue 576 of p70. This 
finding suggests that the inhibitory activity of p70 can be regulated by 
signaling via the adenylate cyclase pathway.