PMID- 10469655
OWN - NLM
STAT- MEDLINE
DCOM- 19991028
LR  - 20191210
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 17
DP  - 1999 Sep 1
TI  - NF-kappaB p105 is a target of IkappaB kinases and controls signal induction of
      Bcl-3-p50 complexes.
PG  - 4766-78
AB  - The NF-kappaB precursor p105 has dual functions: cytoplasmic retention of
      attached NF-kappaB proteins and generation of p50 by processing. It is poorly
      understood whether these activities of p105 are responsive to signalling
      processes that are known to activate NF-kappaB p50-p65. We propose a model that
      p105 is inducibly degraded, and that its degradation liberates sequestered
      NF-kappaB subunits, including its processing product p50. p50 homodimers are
      specifically bound by the transcription activator Bcl-3. We show that TNFalpha,
      IL-1beta or phorbolester (PMA) trigger rapid formation of Bcl-3-p50 complexes
      with the same kinetics as activation of p50-p65 complexes. TNF-alpha-induced
      Bcl-3-p50 formation requires proteasome activity, but is independent of p50-p65
      released from IkappaBalpha, indicating a pathway that involves p105 proteolysis. 
      The IkappaB kinases IKKalpha and IKKbeta physically interact with p105 and
      inducibly phosphorylate three C-terminal serines. p105 is degraded upon TNF-alpha
      stimulation, but only when the IKK phospho-acceptor sites are intact.
      Furthermore, a p105 mutant, lacking the IKK phosphorylation sites, acts as a
      super-repressor of IKK-induced NF-kappaB transcriptional activity. Thus, the
      known NF-kappaB stimuli not only cause nuclear accumulation of p50-p65
      heterodimers but also of Bcl-3-p50 and perhaps further transcription activator
      complexes which are formed upon IKK-mediated p105 degradation.
FAU - Heissmeyer, V
AU  - Heissmeyer V
AD  - Max-Delbruck-Center for Molecular Medicine, MDC, Robert-Rossle-Strasse 10,
      D-13122 Berlin, Germany.
FAU - Krappmann, D
AU  - Krappmann D
FAU - Wulczyn, F G
AU  - Wulczyn FG
FAU - Scheidereit, C
AU  - Scheidereit C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (B-Cell Lymphoma 3 Protein)
RN  - 0 (BCL3 protein, human)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Protein Precursors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
SB  - IM
MH  - B-Cell Lymphoma 3 Protein
MH  - Cell Line
MH  - Dimerization
MH  - HeLa Cells
MH  - Humans
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins/*metabolism
MH  - Models, Biological
MH  - Models, Genetic
MH  - NF-kappa B/*metabolism
MH  - NF-kappa B p50 Subunit
MH  - Phosphorylation
MH  - Plasmids
MH  - Protein Precursors/metabolism
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - *Signal Transduction
MH  - Time Factors
MH  - Transcription Factors
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC1171549
EDAT- 1999/09/02 00:00
MHDA- 1999/09/02 00:01
CRDT- 1999/09/02 00:00
PHST- 1999/09/02 00:00 [pubmed]
PHST- 1999/09/02 00:01 [medline]
PHST- 1999/09/02 00:00 [entrez]
AID - 10.1093/emboj/18.17.4766 [doi]
PST - ppublish
SO  - EMBO J. 1999 Sep 1;18(17):4766-78. doi: 10.1093/emboj/18.17.4766.