PMID- 10514433
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 42
DP  - 1999 Oct 15
TI  - Molecular dissection of the interactions among IkappaBalpha, FWD1, and Skp1
      required for ubiquitin-mediated proteolysis of IkappaBalpha.
PG  - 29641-7
AB  - The SCF complex containing Skp1, Cul1, and the F-box protein FWD1 (the mouse
      homologue of Drosophila Slimb and Xenopus beta-TrCP) functions as the ubiquitin
      ligase for IkappaBalpha. FWD1 associates with Skp1 through the F-box domain and
      also recognizes the conserved DSGXXS motif of IkappaBalpha. The structural
      requirements for the interactions of FWD1 with IkappaBalpha and with Skp1 have
      now been investigated further. The D31A mutation (but not the G33A mutation) in
      the DSGXXS motif of IkappaBalpha abolished the binding of IkappaBalpha to FWD1
      and its subsequent ubiquitination without affecting the phosphorylation of
      IkappaBalpha. The IkappaBalpha mutant D31E still exhibited binding to FWD1 and
      underwent ubiquitination. These results suggest that, in addition to
      site-specific phosphorylation at Ser(32) and Ser(36), an acidic amino acid at
      position 31 is required for FWD1-mediated ubiquitination of IkappaBalpha.
      Deletion analysis of Skp1 revealed that residues 61-143 of this protein are
      required for binding to FWD1. On the other hand, the highly conserved residues
      Pro(149), Ile(160), and Leu(164) in the F-box domain of FWD1 were dispensable for
      binding to Skp1. Together, these data delineate the structural requirements for
      the interactions among IkappaBalpha, FWD1, and Skp1 that underlie substrate
      recognition by the SCF ubiquitin ligase complex.
FAU - Hattori, K
AU  - Hattori K
AD  - Department of Molecular Biology, Medical Institute of Bioregulation, Kyushu
      University, Fukuoka 812-8582, Japan.
FAU - Hatakeyama, S
AU  - Hatakeyama S
FAU - Shirane, M
AU  - Shirane M
FAU - Matsumoto, M
AU  - Matsumoto M
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 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 0 (Ubiquitins)
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - GTP-Binding Proteins/genetics/*metabolism
MH  - Humans
MH  - Hydrolysis
MH  - *I-kappa B Proteins
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - NF-KappaB Inhibitor alpha
MH  - S-Phase Kinase-Associated Proteins
MH  - Sequence Homology, Amino Acid
MH  - Ubiquitins/*metabolism
MH  - beta-Transducin Repeat-Containing Proteins
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - 10.1074/jbc.274.42.29641 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 15;274(42):29641-7. doi: 10.1074/jbc.274.42.29641.