Transcriptional activation by NF-kappaB requires multiple coactivators.
Nuclear factor-kappaB (NF-kappaB) plays a role in the transcriptional regulation of genes involved in inflammation and cell survival. In this report we demonstrate that NF-kappaB recruits a coactivator complex that has striking similarities to that recruited by nuclear receptors. Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein (CBP), members of the p160 family of coactivators, or the CBP-associated factor (p/CAF) by nuclear antibody microinjection prevents NF-kappaB-dependent transactivation. Like nuclear receptor-dependent gene expression, NF-kappaB-dependent gene expression requires specific LXXLL motifs in one of the p160 family members, and enhancement of NF-kappaB activity requires the histone acetyltransferase (HAT) activity of p/CAF but not that of CBP. This coactivator complex is differentially recruited by members of the Rel family. The p50 homodimer fails to recruit coactivators, although the p50-p65 heterodimeric form of the transcription factor assembles the integrator complex. These findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.
Sheppard
K A
KA
Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Rose
D W
DW
Haque
Z K
ZK
Kurokawa
R
R
McInerney
E
E
Westin
S
S
Thanos
D
D
Rosenfeld
M G
MG
Glass
C K
CK
Collins
T
T
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D051548:Histone Acetyltransferases; D016328:NF-kappa B; D056920:Nuclear Receptor Coactivator 1; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor