REL-ASSOCIATED PP40 - AN INHIBITOR OF THE REL FAMILY OF TRANSCRIPTION FACTORS

The Rel-associated protein pp40 is functionally related to I-kappa-B, an inhibitor of the transcription factor NF-kappa-B. Purified pp40 inhibits the DNA binding activity of the NF-kappa-B protein complex (p50:p65 heterodimers), p50:c-Rel heteromers, and c-Rel homodimers. The sequence of the complementary DNA encoding pp40 revealed similarity to the gene encoding MAD-3, a protein with mammalian I-kappa-B-like activity. Protein sequencing of I-kappa-B purified from rabbit lung confirmed that MAD-3 encodes a protein similar to I-kappa-B. The sequence similarity between MAD-3 and pp40 includes a casein kinase II and consensus tyrosine phosphorylation site, as well as five repeats of a sequence found in the human erythrocyte protein ankyrin. These results suggest that rel-related transcription factors, which are capable of cytosolic to nuclear translocation, may be held in the cytosol by interaction with related cytoplasmic anchor molecules.