PMID- 10497169
OWN - NLM
STAT- MEDLINE
DCOM- 19991102
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 40
DP  - 1999 Oct 1
TI  - Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and
      IkappaBepsilon mediated by the F-box protein FWD1.
PG  - 28169-74
AB  - FWD1 (the mouse homolog of Drosophila Slimb and Xenopus betaTrCP, a member of the
      F-box- and WD40 repeat-containing family of proteins, and a component of the SCF 
      ubiquitin ligase complex) was recently shown to interact with IkappaBalpha and
      thereby to promote its ubiquitination and degradation. This protein has now been 
      shown also to bind to IkappaBbeta and IkappaBepsilon as well as to induce their
      ubiquitination and proteolysis. FWD1 was shown to recognize the conserved
      DSGPsiXS motif (where Psi represents the hydrophobic residue) present in the
      NH(2)-terminal regions of these three IkappaB proteins only when the component
      serine residues are phosphorylated. However, in contrast to IkappaBalpha and
      IkappaBbeta, the recognition site in IkappaBepsilon for FWD1 is not restricted to
      the DSGPsiXS motif; FWD1 also interacts with other sites in the NH(2)-terminal
      region of IkappaBepsilon. Substitution of the critical serine residues in the
      NH(2)-terminal regions of IkappaBalpha, IkappaBbeta, and IkappaBepsilon with
      alanines also markedly reduced the extent of FWD1-mediated ubiquitination of
      these proteins and increased their stability. These data indicate that the three 
      IkappaB proteins, despite their substantial structural and functional
      differences, all undergo ubiquitination mediated by the SCF(FWD1) complex. FWD1
      may thus play an important role in NF-kappaB signal transduction through
      regulation of the stability of multiple IkappaB proteins.
FAU - Shirane, M
AU  - Shirane M
AD  - Department of Molecular Biology, Medical Institute of Bioregulation, Kyushu
      University, Fukuoka 812-8582, Japan.
FAU - Hatakeyama, S
AU  - Hatakeyama S
FAU - Hattori, K
AU  - Hattori K
FAU - Nakayama, K
AU  - Nakayama K
FAU - Nakayama, K
AU  - Nakayama K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (BTRC protein, human)
RN  - 0 (Btrc protein, mouse)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Ubiquitins)
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - GTP-Binding Proteins/*metabolism
MH  - Humans
MH  - Hydrolysis
MH  - I-kappa B Proteins/chemistry/genetics/*metabolism
MH  - Mice
MH  - Mutagenesis
MH  - Phosphorylation
MH  - Sequence Homology, Amino Acid
MH  - Ubiquitins/*metabolism
MH  - beta-Transducin Repeat-Containing Proteins
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
AID - 10.1074/jbc.274.40.28169 [doi]
AID - S0021-9258(19)52032-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 1;274(40):28169-74. doi: 10.1074/jbc.274.40.28169.