Biomedical Engineering Reference
In-Depth Information
5
Regulation of Nuclear
NF-
B Action: A Key Role
for Posttranslational
Modification
κ
Lin-Feng Chen and Warner C. Greene
CONTENTS
5.1
5.2
Phosphorylation as a Key Regulator of NF-
κ
B Action ................................ 88
5.3
NF-
κ
B and Acetylation .................................................................................. 91
5.3.1
Acetylation of p65 ............................................................................. 92
5.3.2
Acetylation of p50 ............................................................................. 95
5.4
Histone Acetylation Regulates NF-
κ
B Gene Activation ............................... 95
5.5
B Target Genes ............................. 97
Histone Phosphorylation Activates NF-
κ
5.1
INTRODUCTION
The NF-
B/Rel family of transcription factors plays a central role in governing
diverse biological processes, ranging from the inflammatory and immune responses
to cellular proliferation, differentiation, and survival. Since its discovery in 1986,
NF-
κ
B has been one of the most intensely studied transcription factors in eukaryotic
biology. Each of the seven mammalian NF-
κ
κ
B/Rel-related proteins contains an N-
terminal Rel homology domain (RHD), as discussed in
Chapter 2
, which mediates
DNA binding, dimerization, and interaction with the I
B family proteins. P65, c-
Rel, and RelB contain C-terminal transactivation domains (TADs), while p50 and
p52 proteins lack these regions. As such, the binding of p50 and p52 homodimers
can repress
κ
B-specific transcription involving the recruitment of different corepres-
sors [1]. The prototypical NF-
κ
κ
B complex is a heterodimer of p50 and p65. However,
NF-
B/Rel family members can form different homo- or heterodimers that likely
confer a degree of target gene specificity [2].
κ
87
