F-box proteins everywhere
Introduction
Regulation of protein stability through the ubiquitin proteasome system (UPS) is an important mechanism that underlies numerous cellular and organismal processes [1]. Degradation via the UPS is a two-step process: the protein is first tagged by covalent attachment of ubiquitin and subsequently degraded by a multicatalytic protease complex called the 26S proteasome. The ubiquitin conjugation pathway involves several classes of enzymes, the most interesting being the ubiquitin protein ligases (or E3s) that are in charge of the substrate specificity. To date, several hundred different E3s have been predicted in sequenced metazoan and plant genomes, on the basis of commonly shared structural motifs. These E3s fall into different families, among which the SCF (SKP1-CUL1-F-box) is the largest and best characterised.
The SCF complex is composed of four major subunits: Cullin 1 (CUL1), SUPPRESSOR OF KINETOCHORE PROTEIN 1 (SKP1), RING-BOX 1 (RBX1)/REGULATOR OF CULLINS 1 (ROC1) and an F-box protein ([2•]; Figure 1). Structure–function studies in yeast and mammals have demonstrated that CUL1 functions as a scaffold in assembling the different subunits of the complex. Thus, CUL1 interacts at its carboxyl terminus with the RING-domain protein RBX1 (forming the core catalytic domain) and, at its amino terminus, with the adaptor protein SKP1, which links to one of the several F-box proteins. F-box proteins, in addition to the loosely conserved F-box motif that binds to SKP1, usually carry one of a variety of typical protein–protein interaction domains that confers substrate specificity to the SCF complexes. This review emphasizes important recent research on the function of F-box proteins in various aspects of plant biology (Table 1).
Section snippets
Dynamic assembly of a multiprotein complex
In plants, the so-called CUL1 (e.g. Arabidopsis AtCUL1) is phylogenetically distant from yeast or metazoan CUL1 members and falls into a separate phylogenetic clade [3]. Unlike vertebrates, but like Caenorhabditis and Drosophila, Arabidopsis also encodes a large family of Arabidopsis SKP1-LIKE (ASK) proteins [4]. Among the 21 members of this family, ASK1 and ASK2 seem to play prominent roles in plant SCF complexes. This is supported by the fact that they are the most conserved SKP1-related
F-box proteins in plant hormone response pathways
Indole-3-acetic acid (IAA or auxin) is involved in many aspects of plant development and was the first phytohormone whose signalling pathway was shown to involve an SCF complex. The F-box protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1) is part of an SCF complex that mediates auxin-dependant transcriptional control by targeting certain AUX/IAA proteins for ubiquitin-dependant degradation [13]. AUX/IAA proteins serve as repressors of auxin action by binding to and blocking the AUXIN RESPONSE FACTOR
F-box proteins in lateral root formation
Several F-box proteins have been implicated in organ formation and development. These proteins include UNUSUAL FLORAL ORGANS (UFO) and FIMBRIATA (FIM), which control multiple aspects of floral development [35, 36, 37], and MAX2, which represses shoot lateral branching [38]. As auxin plays a pivotal role in almost every aspect of plant development, it is perhaps not surprising that a mutant that has a defect in the Arabidopsis F-box protein TIR1 is deficient in lateral root formation [39].
F-box proteins in light signalling and clock control
F-box proteins have been implicated in phytochrome A (phyA)-dependant light signalling. Mutants that have defects in the F-box-protein encoding gene EMPFINDLICHER IM DUNKELROTEN LICHT (EID1) exhibit increased far-red light sensitivity and, thus, it has been proposed that an SCFEDI1 E3 targets positive phyA signal transducers(s) for proteolysis [42]. Moreover, EID1 modulates phyA-dependant light responses during all stages of plant development [43]. ATTENUATED FAR-RED RESPONSE (AFR) is another
F-box proteins in pollen recognition and rejection
Self-incompatibility interactions in Solanaceae, Scrophulariaceae and Rosaceae, which prevent inbreeding, are controlled by pistil-expressed S-RNases that act as cytotoxins to inhibit the growth of pollen that has a matching S-allele [51]. Strikingly, clusters of F-box genes known as SFB or SLF (S-linked F-box genes) have recently been found close to the S-RNase genes in Petunia, and these genes have been proposed to control specificity on the pollen side [52••]. A role for an F-box protein,
F-box proteins encoded by plant pathogenic microbes
It is well established that animal viruses manipulate the UPS to favour their infection [57]. In some cases, viruses directly encode E3 components, whereas in others, host E3s are redirected to serve viral purposes. Interestingly, two plant viruses have been found to encode F-box proteins. The Faba bean necrotic yellow virus protein CELL CYCLE LINK (CLINK) contains an F-box motif and binds to MsSKP1, an alfalfa SKP1 homologue [58]. The function of CLINK has not yet been established but it is
Conclusions and perspectives
If the nearly 700 predicted Arabidopsis F-box proteins [7] all form SCF complexes, it is evident that we are still very far from having an integrated picture of their functional repertory. Conditional mutants that affect core components of the SCF, such as the recently described auxin response 6-3 (axr6-3) allele of AtCUL1 provide further evidence that novel pathways that are regulated by SCFs remain to be characterized [62]. Elucidation of these pathways, at the molecular level, will certainly
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
EL, AV, TP and PG are supported by the Centre National de Recherche Scientifique (CNRS) and a grant from the French Ministry of Research (ACI 2004 N°BCMS 167). PA is supported by EMBO grant ALTF 414-2005. We thank Kenneth Richards for critical reading of the article.
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