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J Biol Chem, Vol. 274, Issue 12, 7941-7945, March 19, 1999
B
by the Proteasome Requires
Interaction with the F-box Protein h-
TrCP
,
,,,, and
From the Activation of NF- Unité d'Immunologie Virale and
Groupe des Bunyaviridés, Unité des arbovirus et
virus des fièvres hémorragiques, Institut Pasteur, 25 et
28, rue du Dr. Roux, 75724 Paris Cedex 15, France and the
¶ Institut Cochin de Génétique Moléculaire
(ICGM) INSERM CJF9703 and ** ICGM U129 INSERM, Université Paris V,
75014 Paris, France
B transcription factors
requires phosphorylation and ubiquitin-proteasome-dependent
degradation of IB proteins. We provide evidence that a human F-box
protein, h-
TrCP, a component of Skp1-Cullin-F-box protein (SCF)
complexes, a new class of E3 ubiquitin ligases, is essential for
inducible degradation of IB
. TrCP associates with
Ser32-Ser36 phosphorylated, but not with
unmodified IB or Ser32-Ser36
phosphorylation-deficient mutants. Expression of a F-box-deleted TrCP inhibits IB degradation, promotes accumulation of
phosphorylated Ser32-Ser36 IB, and
prevents NF-B-dependent transcription. Our findings indicate that TrCP is the adaptor protein required for IB
recognition by the SCF
TrCP E3 complex that ubiquitinates
IB and makes it a substrate for the proteasome.
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