PMID- 15214841
OWN - NLM
STAT- MEDLINE
DCOM- 20050222
LR  - 20240322
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 382
IP  - Pt 2
DP  - 2004 Sep 1
TI  - Functions of NF-kappaB1 and NF-kappaB2 in immune cell biology.
PG  - 393-409
AB  - Two members of the NF-kappaB (nuclear factor kappaB)/Rel transcription factor 
      family, NF-kappaB1 and NF-kappaB2, are produced as precursor proteins, NF-kappaB1 
      p105 and NF-kappaB2 p100 respectively. These are proteolytically processed by the 
      proteasome to produce the mature transcription factors NF-kappaB1 p50 and 
      NF-kappaB2 p52. p105 and p100 are known to function additionally as IkappaBs 
      (inhibitors of NF-kappaB), which retain associated NF-kappaB subunits in the 
      cytoplasm of unstimulated cells. The present review focuses on the latest 
      advances in research on the function of NF-kappaB1 and NF-kappaB2 in immune 
      cells. NF-kappaB2 p100 processing has recently been shown to be stimulated by a 
      subset of NF-kappaB inducers, including lymphotoxin-beta, B-cell activating 
      factor and CD40 ligand, via a novel signalling pathway. This promotes the nuclear 
      translocation of p52-containing NF-kappaB dimers, which regulate peripheral 
      lymphoid organogenesis and B-lymphocyte differentiation. Increased p100 
      processing also contributes to the malignant phenotype of certain T- and B-cell 
      lymphomas. NF-kappaB1 has a distinct function from NF-kappaB2, and is important 
      in controlling lymphocyte and macrophage function in immune and inflammatory 
      responses. In contrast with p100, p105 is constitutively processed to p50. 
      However, after stimulation with agonists, such as tumour necrosis factor-alpha 
      and lipopolysaccharide, p105 is completely degraded by the proteasome. This 
      releases associated p50, which translocates into the nucleus to modulate target 
      gene expression. p105 degradation also liberates the p105-associated MAP kinase 
      (mitogen-activated protein kinase) kinase kinase TPL-2 (tumour progression 
      locus-2), which can then activate the ERK (extracellular-signal-regulated 
      kinase)/MAP kinase cascade. Thus, in addition to its role in NF-kappaB 
      activation, p105 functions as a regulator of MAP kinase signalling.
FAU - Beinke, Soren
AU  - Beinke S
AD  - Division of Immune Cell Biology, MRC National Institute for Medical Research, 
      Mill Hill, London NW7 1AA, UK.
FAU - Ley, Steven C
AU  - Ley SC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Transcription Factor RelA)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Immune System/*physiology
MH  - NF-kappa B/*physiology
MH  - NF-kappa B p50 Subunit
MH  - Transcription Factor RelA
PMC - PMC1133795
EDAT- 2004/06/25 05:00
MHDA- 2005/02/23 09:00
PMCR- 2005/03/01
CRDT- 2004/06/25 05:00
PHST- 2004/06/24 00:00 [accepted]
PHST- 2004/06/22 00:00 [revised]
PHST- 2004/04/02 00:00 [received]
PHST- 2004/06/25 05:00 [pubmed]
PHST- 2005/02/23 09:00 [medline]
PHST- 2004/06/25 05:00 [entrez]
PHST- 2005/03/01 00:00 [pmc-release]
AID - BJ20040544 [pii]
AID - bj3820393 [pii]
AID - 10.1042/BJ20040544 [doi]
PST - ppublish
SO  - Biochem J. 2004 Sep 1;382(Pt 2):393-409. doi: 10.1042/BJ20040544.