M. Kroll et al., Inducible degradation of I kappa B alpha by the proteasome requires interaction with the F-box protein h-beta TrCP, J BIOL CHEM, 274(12), 1999, pp. 7941-7945
Activation of NF-kappa B transcription factors requires phosphorylation and
ubiquitin-proteasome-dependent degradation of I kappa B proteins. We provi
de evidence that a human F-box protein, h-beta TrCP, a component of Skp1-Cu
llin-F-box protein (SCF) complexes, a new class of E3 ubiquitin ligases, is
essential for inducible degradation of I kappa B alpha. beta TrCP associat
es with Ser(32)-Ser(36) phosphorylated, but not with unmodified I kappa B a
lpha or Ser(32)-Ser(36) phosphorylation-deficient mutants. Expression of a
F-box-deleted beta TrCP inhibits I kappa B alpha degradation, promotes accu
mulation of phosphorylated Ser(32)-Ser(36) I kappa B alpha, and prevents NF
-kappa B-dependent transcription. Our findings indicate that beta TrCP is t
he adaptor protein required for I kappa B alpha recognition by the SCFbeta
TrCP E3 complex that ubiquitinates I kappa B alpha and makes it a substrate
for the proteasome.