F-box proteins everywhere

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The ubiquitin proteasome system is a key regulator of many biological processes in all eukaryotes. This mechanism employs several types of enzymes, the most important of which are the ubiquitin E3 ligases that catalyse the attachment of polyubiquitin chains to target proteins for their subsequent degradation by the 26S proteasome. Among the E3 families, the SCF is the best understood; it consists of a multi-protein complex in which the F-box protein plays a crucial role by recruiting the target substrate. Strikingly, nearly 700 F-box proteins have been predicted in Arabidopsis, suggesting that plants have the capacity to assemble a multitude of SCF complexes, possibly controlling the stability of hundreds of substrates involved in a plethora of biological processes. Interestingly, viruses and even pathogenic bacteria have also found ways to hijack the plant SCF and to reprogram it for their own purposes.

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.

References (68)

  • J. Smalle et al.

    The ubiquitin 26S proteasome proteolytic pathway

    Annu Rev Plant Biol

    (2004)
  • M.D. Petroski et al.

    Function and regulation of cullin-RING ubiquitin ligases

    Nat Rev Mol Cell Biol

    (2005)
  • W.H. Shen et al.

    Null mutation of AtCUL1 causes arrest in early embryogenesis in Arabidopsis

    Mol Biol Cell

    (2002)
  • H. Kong et al.

    Highly heterogeneous rates of evolution in the SKP1 gene family in plants and animals: functional and evolutionary implication

    Mol Biol Evol

    (2004)
  • E.P. Risseeuw et al.

    Protein interaction analysis of SCF ubiquitin E3 ligase subunits from Arabidopsis

    Plant J

    (2003)
  • F. Liu et al.

    The ASK1 and ASK2 genes are essential for Arabidopsis early development

    Plant Cell

    (2004)
  • J.M. Gagne et al.

    The F-box subunit of the SCF E3 complex is encoded by a diverse superfamily of genes in Arabidopsis

    Proc Natl Acad Sci USA

    (2002)
  • G. Parry et al.

    Regulation of cullin-based ubiquitin ligases by the Nedd8/RUB ubiquitin-like proteins

    Semin Cell Dev Biol

    (2004)
  • C. Schwechheimer

    The COP9 signalosome (CSN): an evolutionary conserved proteolysis regulator in eukaryotic development

    Biochim Biophys Acta

    (2004)
  • S. Feng et al.

    Arabidopsis CAND1, an unmodified CUL1-interacting protein, is involved in multiple developmental pathways controlled by ubiquitin/proteasome-mediated protein degradation

    Plant Cell

    (2004)
  • W.M. Gray et al.

    Auxin regulates SCF(TIR1)-dependent degradation of AUX/IAA proteins

    Nature

    (2001)
  • N. Dharmasiri et al.

    Auxin signaling and regulated protein degradation

    Trends Plant Sci

    (2004)
  • N. Dharmasiri et al.

    The F-box protein TIR1 is an auxin receptor

    Nature

    (2005)
  • S. Kepinski et al.

    The Arabidopsis F-box protein TIR1 is an auxin receptor

    Nature

    (2005)
  • N. Dharmasiri et al.

    Plant development is regulated by a family of auxin receptor F box proteins

    Dev Cell

    (2005)
  • L. Navarro et al.

    A plant miRNA contributes to antibacterial resistance by repressing auxin signaling

    Science

    (2006)
  • D.X. Xie et al.

    COI1: an Arabidopsis gene required for jasmonate-regulated defense and fertility

    Science

    (1998)
  • K.M. McGinnis et al.

    The Arabidopsis SLEEPY1 gene encodes a putative F-box subunit of an SCF E3 ubiquitin ligase

    Plant Cell

    (2003)
  • A. Dill et al.

    The Arabidopsis F-box protein SLEEPY1 targets gibberellin signaling repressors for gibberellin-induced degradation

    Plant Cell

    (2004)
  • L.C. Strader et al.

    Recessive-interfering mutations in the gibberellin signaling gene SLEEPY1 are rescued by overexpression of its homologue, SNEEZY

    Proc Natl Acad Sci USA

    (2004)
  • A. Sasaki et al.

    Accumulation of phosphorylated repressor for gibberellin signaling in an F-box mutant

    Science

    (2003)
  • S.G. Thomas et al.

    Update on gibberellin signaling. A tale of the tall and the short

    Plant Physiol

    (2004)
  • P. Achard et al.

    Integration of plant responses to environmentally activated phytohormonal signals

    Science

    (2006)
  • X. Fu et al.

    The Arabidopsis mutant sleepy1 gar2-1 protein promotes plant growth by increasing the affinity of the SCFSLY1 E3 ubiquitin ligase for DELLA protein substrates

    Plant Cell

    (2004)
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