Plant Molecular Biology 44: 123–128, 2000.
© 2000 Kluwer Academic Publishers. Printed in the Netherlands.
F-box proteins and protein degradation: An emerging theme in cellular
J. Carlos del Pozo and Mark Estelle
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA (
for correspondence; e-mail: email@example.com)
Received 30 May 2000; accepted in revised form 28 July 2000
Selective protein degradation by the ubiquitin-proteosome pathway has recently emerged as a powerful regulatory
mechanism in a wide variety of cellular processes. Ubiquitin conjugation requires the sequential activity of three
enzymes or protein complexes called the ubiquitin-activating enzyme (E1), the ubiquitin-conjugatingenzyme (E2),
and the ubiquitin-protein ligase (E3). In most eukaryotes, there are a small number of similar E1 isoforms without
apparent functional speciﬁcity. The speciﬁc selection of target proteins is accomplished by the E2 and E3 proteins.
One of the best-characterized families of E3s are the SCF complexes. The SCF is composed of a cullin (Cdc53),
SKP1, RBX1 and one member of a large family of proteins called F-box proteins. The function of the F-box
protein is to interact with target proteins. In some cases, the stability of the F-box protein may regulate activity
of the SCF complex. In addition, post-translational modiﬁcation of the cullin subunit by the ubiquitin-like protein
RUB/NEDD8 appears to regulate SCF function. In plants, the SCF has so far been implicated in ﬂoral development,
circadian clock, and response to the plant growth regulators auxin and jasmonic acid.
Regulated protein degradation by the ubiquitin-
proteosome pathway has an important role in diverse
cellular processes including cell cycle regulation and
signal transduction (Hershko and Ciechanover, 1998).
The ubiquitin-conjugation pathway involves the ac-
tivity of three enzymes or protein complexes called
the ubiquitin-activating enzyme (E1), the ubiquitin-
conjugating enzyme (E2) and the ubiquitin-protein
ligase (E3) (Hershko and Ciechanover, 1998). The E1
enzyme catalyzes the formation of a thiolester bond
between the COOH-terminus of ubiquitin and a con-
served cysteine within the E1 enzyme. The ubiquitin
moiety is then transferred to an E2 enzyme, again
forming a thiol-ester bond with a conserved cysteine.
Next, the E3 enzyme facilitates the formation of an
isopeptide linkage between ubiquitin and the target
protein. A polyubiquitin chain is subsequently formed
by the addition of ubiquitin monomers via an inter-
nal lysine residue within the ubiquitin protein. This
polyubiquitin chain is recognized by the proteosome,
the target is degraded, and ubiquitin monomers are
Eukaryotic organisms contain a small number of
similar E1 isoforms with no apparent functional speci-
ﬁcity. The E2 family is larger and several E2 enzymes
have specialized cellular functions. In the case of the
E3 ligases, the picture is much more complicated. The
E3 can be a single polypeptide or a multisubunit com-
plex. At present, three different kinds of E3 complexes
have been described called SCF, APC, and pVHL (Pat-
ton et al., 1998; Peters, 1998; Deshaies, 1999; Pause
et al., 1999). In this review we will focus on the or-
ganization and regulation of the SCF ubiquitin-protein
Architecture of the SCF
The SCF complex is composed of four subunits:
cullin (Cdc53 in yeast), SKP1, RBX1 and an F-
box protein (Patton et al., 1998; Deshaies, 1999).
The ﬁrst three proteins form a common scaffold onto