The rel-associated pp40 protein prevents DNA binding of Rel and NF-kappa B: relationship with I kappa B beta and regulation by phosphorylation.
The product of proto-oncogene Rel associates with a number of cellular proteins. We have studied the effect of one of them, a phosphoprotein of 40 kD (pp40), on the DNA-binding activity of the Rel protein. We demonstrate that purified pp40 not only inhibits the binding of Rel, but also NF-kappa B (p50-p65) heterocomplex to DNA. Additionally, I kappa B beta, but not I kappa B alpha, also prevented the binding of Rel to the kappa B site. I kappa B beta and pp40 are related proteins because (1) they share a number of common tryptic peptides, (2) their inhibitory effect on DNA binding can be abolished by preincubation with pp40-specific antiserum, and (3) labeled I kappa B beta can be immunoprecipitated with pp40 antibodies. pp40 is part of the Rel complex present in the cytoplasm and nuclear extracts of WEHI-231 cells. The activity of pp40 to inhibit the DNA binding of Rel and NF-kappa B is modulated by phosphorylation.
Kerr
L D
LD
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186-5800.
Inoue
J
J
Davis
N
N
Link
E
E
Baeuerle
P A
PA
Bose
H R
HR
Verma
I M
IM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006706:Homeostasis; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D015345:Oligonucleotide Probes; D010446:Peptide Fragments / Q000302:isolation & purification; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D011519:Proto-Oncogenes; D012097:Repressor Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D012097:Repressor Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C