Plants express both passive and active defense mechanisms. This proposal focuses on active defense mediated by one branch of the plant immune system—the so-called “specific disease resistance” branch (Dangl and Jones, 2001). The plant immune system consists of two mechanistically related branches. The first guides responses to “generic” pathogen molecules that are evolutionarily constrained to maintain a core microbial function. These are termed Pathogen Associated Molecular Patterns (PAMPs) and have been shown to be key regulators of mammalian immune responses. In plants, PAMP-like molecules include a peptide derived from flagellin, LPS, pathogen-encoded transglutaminase and xylanase proteins, and remarkably, a translational elongation factor EF-Tu (reviewed in (Gomez-Gomez and Boller, 2002)). These PAMPs elicit stereotypic plant cellular defense responses, like anion and calcium fluxes, and large scale transcriptional and biosynthetic re-programming. In at least one case this response contributes to restriction of pathogen growth (Zipfel et al., 2004). PAMP-driven transcriptional re-programming looks to be generic, meaning that the same global changes occur following stimulation with either of two different PAMPs (Navarro et al., 2004; Tao et al., 2003). Recognition requires, thus far, plant extracellular Leucine Rich Repeat (LRR) receptor like proteins, and there is at least one case of direct binding of xylanase to the genetically defined LRR receptor (Gómez-Gómez and Boller, 2000; Ron and Avni, 2004). There is limited functional polymorphism in both the PAMPs and their known receptors, consistent with this branch of the plant immune system being ancient and slowly evolving.

Yet pathogens that express PAMPS are demonstrably successful, so they must have evolved virulence mechanisms that allow them to evade, dampen or disrupt basal defense. Plant pathogenic bacteria, for example, deliver 15-30 proteins into host cells via an evolutionarily conserved type III secretion system (also used by animal pathogens in host colonization; (Alfano and Collmer, 2004; Chang et al., 2005)). Importantly, a Pseudomonas syringae (Pto) strain mutated in the type III secretion system (Pto DC3000hrcC), and unable to deliver any type III effectors, actually drives a more rapid and higher amplitude transcriptional re-programming than does the isogenic wild type strain (Jakobek et al., 1993). Hence, the sum of the Pto DC3000 type III effector proteins must block the basal defense response sufficiently to allow successful colonization. Recent studies have, in fact, corroborated this supposition (DebRoy et al., 2004; Hauck et al., 2003; Jamir et al., 2004; Zhao et al., 2003). Also, the transcriptional profile of Pto DC3000hrcC is largely overlapping with that of any pure PAMP tested to date (Navarro et al., 2004; Tao et al., 2003).

The evolution of virulence mechanisms that help pathogens overcome basal defense responses is likely responsible for the evolution of “specific disease resistance” in plants. These gene-for-gene systems constitute the second branch of the plant immune system (Dangl and Jones, 2001). Here, successful resistance in the host is polymorphic, and disease resistance (R) gene alleles require the simultaneous presence of a gene in the pathogen to trigger their action. The pathogen genes were called avirulence (avr) genes, because their presence rendered a particular pathogen strain avirulent on a particular host. However, and again focusing on pathogenic bacteria, several avr genes contribute positively to pathogen virulence on genetically susceptible hosts (r). It is perhaps unsurprising to find that the avr genes encode type III effectors (reviewed in (Alfano and Collmer, 2004; Nimchuk et al., 2001))! Thus, a fair generalization is that among the suite of virulence factors (type III effectors) delivered by pathogenic bacteria into the host, several find targets and contribute to virulence. But if one of them is “recognized” by the corresponding R protein, then disease resistance is the result. This specific, R-mediated disease resistance is accompanied by a massive extracellular oxidative burst, a much accelerated and higher amplitude transcriptional re-programming, and, in most cases, hypersensitive cell death at and surrounding the infection site (Nimchuk et al., 2003). Importantly, though, the R-mediated transcriptional responses are qualitatively very similar to basal defense responses to Pto DC3000hrcC, just faster and stronger (Tao et al., 2003).

The majority of R genes defined to date encode polymorphic proteins that feature a nucleotide binding site and leucine-rich repeats. NB-LRR proteins also have either coiled-coil (CC) or TIR domains at or near their N-termini in most cases (Dangl and Jones, 2001). NB-LRR proteins “recognize” the products of Avr proteins and are activated in an as yet unknown manner that involves intra-and inter-molecular rearrangements and nucleotide binding (Belkhadir et al., 2004b; Moffett et al., 2002; Rathjen and Moffett, 2003). Pathogens from all kingdoms trigger remarkably similar NB-LRR-mediated defense responses, suggesting that additional, conserved host components participate in the control of NB-LRR protein function. Some, like EDS1 and PAD4, also regulate the basal defense response defined above, and hence allow enhanced growth of virulent pathogens on susceptible (r) hosts (Glazebrook, 2001). Other key components for NB-LRR function are encoded by RAR1 and SGT1, defined by recessive mutations and/or gene silencing in barley, Arabidopsis, potato, tobacco, and tomato (Austin et al., 2002; Azevedo et al., 2002; Liu et al., 2002; Peart et al., 2002; Tornero et al., 2002) (see below). NB-LRR action often leads to increases in local and systemic levels of the plant signaling hormone Salicylic acid (SA) which is required to establish systemic acquired resistance (SAR; (Dong, 1998)). SAR is, in essence, a pre-poised basal defense response that can respond rapidly and at high amplitude to generic secondary infection.

This proposal focuses on Arabidopsis NB-LRR proteins and the bacterial type III effector proteins that trigger their action. We cloned the Arabidopsis RPM1 gene, which encodes a CC-NB-LRR protein that conditions resistance to P. syringae strains expressing either the avrRpm1 or the sequence unrelated avrB type III effectors (Bisgrove et al., 1994; Grant et al., 1995). We demonstrated that avrRpm1 is required for full virulence of some strains of P. syringae (Ritter and Dangl, 1995). The dual specificity encoded suggested that RPM1 may not encode a direct receptor for the relevant pathogen signals. Instead, we proposed that AvrRpm1 and AvrB might target the same host protein complex, leading to RPM1 activation (Grant et al., 1995). RPM1 is a peripheral plasma membrane protein (Boyes et al., 1998). Other NB-LRR proteins, RPS2 and RPS5 have since also been localized to the plasma membrane (Axtell and Staskawicz, 2003; Holt III et al., 2005). AvrRpm1, AvrB and an active auto-catalytic cleavage product of AvrPphB are modified by myristoylation once inside the plant cell and are thus targeted to the plasma membrane (Nimchuk et al., 2000). This eukaryote-specific modification is required for the functions of AvrRpm1 and AvrB, and likely of AvrPphB as well (Shao et al., 2003).

Several NB-LRR proteins appear to recognize type III effectors indirectly, by detecting products of their action on host targets. Indirect interaction of pathogen effector proteins and their corresponding NB-LRR proteins is described by the “guard" hypothesis (Dangl and Jones, 2001; van der Biezen and Jones, 1998). Two tenets of this hypothesis are that 1) a given virulence factor has a target(s) in the host, independent of the corresponding NB-LRR protein; 2) by manipulating this target(s) the virulence factor produces a cellular perturbation that is recognized by the corresponding NB-LRR protein; and 3) that one or more host targets for a given virulence factor might be required for both initiation of R function in resistant plants and for virulence factor function on susceptible plants. RIN4 is a seminal example of a host target of type III effectors that is targeted by pathogen virulence factors and "guarded" by NB-LRR proteins. RIN4 is a small (211aa) membrane associated protein that is targeted by three different type III effector proteins, and associates in vivo with two different NB-LRR proteins from Arabidopsis. Two unrelated type III effectors, AvrRpm1 and AvrB, interact with and induce phosphorylation of RIN4 (Mackey et al., 2002). The perturbation of RIN4 by AvrRpm1 or AvrB is hypothesized to activate RPM1. A third effector, AvrRpt2 also targets RIN4 and induces its post-transcriptional disappearance (Axtell and Staskawicz, 2003; Mackey et al., 2003). AvrRpt2 is a protease that is hypothesized to directly eliminate the RIN4 protein (Axtell et al., 2003). Disappearance of RIN4 activates RPS2, the NB-LRR protein corresponding to AvrRpt2 (Mackey et al., 2003). These results support the first two tenets of the guard hypothesis.

We recently showed that AvrRpt2 or AvrRpm1 manipulate RIN4 and associated proteins in order to inhibit PAMP-induced defense signaling (Kim et al., 2005). Thus, we suggest that plants use RPS2 and RPM1 to "guard" themselves against pathogens that deploy type III effector proteins to inhibit PAMP-signaling.

The generality of these findings is as yet untested, though supporting data are emerging. For example, PBS1 is a proteolytic target of the type III effector, AvrPphB, and RPS5 induces defense responses upon cleavage of PBS1 (Innes, 2004; Shao et al., 2003). Perhaps cleavage of PBS1 contributes to an as yet unidentified virulence activity of AvrPphB. The “Guard Hypothesis” for NB-LRR activation may not be universal. Evolutionary arguments suggest direct interaction of other pathogen Avr proteins (not bacterial type III effectors) with the corresponding NB-LRR proteins in two cases (Allen et al., 2004; Dodds et al., 2004). Further, it is likely that there are two classes of NB-LRR genes: slowly evolving and perhaps stably associated with a host protein they guard, and more rapidly evolving proteins that may be directly interacting with rapidly evolving pathogen proteins in an arms race (Kuang et al., 2004; Van der Hoorn et al., 2002).

At least two additional proteins, RAR1 and SGT1, are required for many NB-LRR functions. Loss of function mutations in RAR1 dramatically reduce steady-state levels of all tested NB-LRR proteins. Thus, RAR1 plays a generic role in maintaining pre-activation NB-LRR protein levels (Belkhadir et al., 2004a; Bieri et al., 2004; Tornero et al., 2002). However, rar1 mutants suppress the resistance function of only a subset of NB-LRR proteins. A "threshold model" was proposed to explain the apparent discrepancy between genetic requirements for RAR1 and its biochemical function. In this model, NB-LRR proteins that are genetically RAR1 "independent" accumulate to relatively high steady state levels, and remain above a threshold required for efficient defense activation even when destabilized in a rar1 background. In contrast, NB-LRR proteins that are genetically RAR1 “dependent” accumulate to relatively low levels and depend on RAR1 to maintain them above the signal competent threshold (Bieri et al., 2004). RAR1 encodes a protein of unknown biochemical function with two novel zinc-binding domains (CHORD I and II; (Shirasu et al., 1999)). RAR1 likely collaborates with cytosolic HSP90, and hence can be considered a co-chaperone in the maintenance of signal competent NB-LRR protein complexes (Hubert et al., 2003). SGT1 was identified both in genetic screens for loss of Peronospora parasitica resistance and through the presence of a CS domain in this protein (Austin et al., 2002; Azevedo et al., 2002; Tör et al., 2002). The CS domain is found in animal homologs of RAR1 but not in plant RAR1 proteins, suggesting that RAR1 and SGT1 would interact physically. They do, and were as a consequence believed to act together (Azevedo et al., 2002). Double mutant analysis also suggested this, at least for RPP5. SGT1 is an essential protein that is a component of the yeast kinetochore, and SGT1 physically interacts with the SCF ubiquitin ligase complex (Kitigawa et al., 1999). While one temperature sensitive allele of SGT1, Scsgt1-3, causes decreased SCF target protein accumulation, another Scsgt1-5, has the opposite effect. Thus in yeast the SGT1 loss-of-function affect on SCF targets is unclear. However, VIGS silencing of SGT1 in tobacco had no effect on R protein accumulation (Moffett et al., 2002). While several experiments in other systems have addressed the phenotypic effects of SGT1 silencing/depletion, none have looked at the protein levels of various presumed targets of SGT1 activity (Dubacq et al., 2002; Steensgaard et al., 2004).

We demonstrated that both RAR1 and SGT1b act antagonistically to control the correct assembly of at least some NB-LRR proteins into a signal competent pre-initiation complex that also is likely to contain HSP90. Several observations support this contention. First, the CS domain shared between SGT1 and animal RAR1 homologs shows predicted structural similarity with the HSP90 co-chaperone, p23 (Dubacq et al., 2002). Second, HSP90 interacts independently with RAR1 and SGT1 in planta, and the HSP90.2 isoform is required for RPM1 function and accumulation (Hubert et al., 2003). Third, plant HSP90 was isolated from independent yeast-two-hybrid screens with RAR1 and SGT1 (Liu et al., 2004; Takahashi et al., 2003). Fourth, silencing of HSP90 blocks N and Pto disease resistance functions (Lu et al., 2003). Fifth, we recently demonstrated that, for at least several NB-LRR proteins, RAR1 and SGT1b antagonize each other to control NB-LRR accumulation and stability (Holt III et al., 2005).

A combination of genetics (forward and reverse), biochemistry and cell biology is necessary to understand how NB-LRR proteins are assembled into a pre-activation, signal competent state and to define how they function after infection. Our Arabidopsis 2010 Project is a multi-disciplinary program to approach those goals. As such, it is an excellent training ground for students at all levels and for post-doctoral fellows.

The genes, proteins, and seed stocks that we have generated and are continuing to generate as part of our Arabidopsis 2010 Project can be found at:

http://www.bio.unc.edu/dangl/lab/projects/index.htm

For more information on the Dangl lab see:

http://www.bio.unc.edu/dangl/lab/

For publications from the Dangl lab, go to:

http://www.bio.unc.edu/dangl/lab/pub/

To contact personnel working on this project (David Hubert, Yijian He, Ben Holt, Mindy Roberts), and others in the Dangl lab, see:

http://www.bio.unc.edu/dangl/lab/people/

References cited in this Introductory essay:

Alfano, J. R., and Collmer, A. (2004). Type III secretion system effector proteins: double agents in bacterial disease and plant defense. Annu Rev Phytopathol 42, 385-414.

Allen, R. L., Bittner-Eddy, P. D., Grenville-Briggs, L. J., Meitz, J. C., Rehmany, A. P., Rose, L. E., and Beynon, J. L. (2004). Host-parasite coevolutionary conflict between Arabidopsis and downy mildew. Science 306, 1957-1960.

Austin, M. J., Muskett, P. J., Kahn, K., Feys, B. J., Jones, J. D. G., and Parker, J. E. (2002). Regulatory role of SGT1 in early R-mediated plant defenses. Science 295, 2077-2080.

Axtell, M. J., Chisholm, S. T., Dahlbeck, D., and Staskawicz, B. J. (2003). Genetic and molecular evidence that the Pseudomonas syringae type III effector protein AvrRpt2 is a cysteine protease. Mol Microbiol 49, 1537-1546.

Axtell, M. J., and Staskawicz, B. J. (2003). Initiation of RPS2-specified disease resistance in Arabidopsis is coupled to the AvrRpt2-directed elimination of RIN4. Cell 112, 369-377.

Azevedo, C., Sadanandom, A., Kitigawa, K., Freialdenhoven, A., Shirasu, K., and Schulze-Lefert, P. (2002). The RAR1 interactor SGT1 is an essential component of R-gene triggered disease resistance. Science 295, 2073-2076.

Belkhadir, Y., Nimchuk, Z., Hubert, D. A., Mackey, D., and Dangl, J. L. (2004a). Arabidopsis RIN4 negatively regulates disease resistance mediated by RPS2 and RPM1 downstream or independent of the NDR1 signal modulator, and is not required for the virulence functions of bacterial type III effectors AvrRpt2 or AvrRpm1. Plant Cell 16, 2822-2835.

Belkhadir, Y., Subramaniam, R., and Dangl, J. L. (2004b). Plant disease resistance protein signaling: NBS-LRR proteins and their partners. Curr Opin Plant Biol 7, 391-399.

Bieri, S., Mauch, S., Shen, Q. H., Peart, J., Devoto, A., Casais, C., Ceron, F., Schulze, S., Steinbiss, H. H., Shirasu, K., and Schulze-Lefert, P. (2004). RAR1 positively controls steady state levels of barley MLA resistance proteins and enables sufficient MLA6 accumulation for effective resistance. Plant Cell 16, 3480-3495.

Bisgrove, S. R., Simonich, M. T., Smith, N. M., Sattler, N. M., and Innes, R. W. (1994). A disease resistance gene in Arabidopsis with specificity for two different pathogen avirulence genes. Plant Cell 6, 927-933.

Boyes, D. C., Nam, J., and Dangl, J. L. (1998). The Arabidopsis thaliana RPM1 disease resistance gene product is a peripheral plasma membrane protein that is degraded coincident with the hypersensitive response. Proc Natl Acad Sci, USA 95, 15849-15854.

Chang, J. H., Urbach, J. M., Law, T. F., Arnold, L. W., Hu, A., Gombar, S., Grant, S. R., Ausubel, F. M., and Dangl, J. L. (2005). A high-throughput, near-saturating screen for type III effector genes from Pseudomonas syringae. Proc Natl Acad Sci U S A 102, 2549-2554.

Dangl, J. L., and Jones, J. D. G. (2001). Plant pathogens and integrated defence responses to infection. Nature 411, 826-833.

DebRoy, S., Thilmony, R., Kwack, Y.-B., Nomura, K., and He, S. Y. (2004). A family of conserved bacterial effectors inhibits salicylic acid-mediated basal immunity and promotes disease necrosis in plants. Proc Natl Acad Sci U S A 101, 9927-9932.

Dodds, P. N., Lawrence, G. J., Catanzariti, A. M., Ayliffe, M. A., and Ellis, J. G. (2004). The Melampsora lini AvrL567 avirulence genes are expressed in haustoria and their products are recognized inside plant cells. Plant Cell 16, 755-768.

Dong, X. (1998). SA, JA, ethylene, and disease resistance in plants. Curr Opin Plant Biol 1, 316-323.

Dubacq, C., Guerois, R., Courbeyrette, R., Kitagawa, K., and Mann, C. (2002). Sgt1p contributes to cyclic AMP pathway activity and physically interacts with the adenylyl cyclase Cyr1p/Cdc35p in budding yeast. Eukaryot Cell 1, 568-582.

Glazebrook, J. (2001). Genes controlling expression of defense responses in Arabidopsis -2001 status. Curr Opin Plant Biol. Gomez-Gomez, L., and Boller, T. (2002). Flagellin perception: a paradigm for innate immunity. Trends Plant Sci 7, 251-256.

Gómez-Gómez, L., and Boller, T. (2000). FLS2: An LRR receptor like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol Cell 5, 1003-1011.

Grant, M. R., Godiard, L., Straube, E., Ashfield, T., Lewald, J., Sattler, A., Innes, R. W., and Dangl, J. L. (1995). Structure of the Arabidopsis RPM1 gene enabling dual specificity disease resistance. Science 269, 843-846.

Hauck, P., Thilmony, R., and He, S. Y. (2003). A Pseudomonas syringae type III effector suppresses cell wall-based extracellular defense in susceptible Arabidopsis plants. Proc Natl Acad Sci U S A 100, 8577-8582.

Holt III, B. F., Belkhadir, Y., and Dangl, J. L. (2005). Antagonistic Control of Disease Resistance Protein Stability in the Plant Immune System. Science 309, 929-932.

Hubert, D. A., Tornero, P., Belkhadir, Y., Krishna, P., Takahashi, A., Shirasu, K., and Dangl, J. L. (2003). Cytosolic HSP90 associates with and modulates the Arabidopsis RPM1 disease resistance protein. Embo J 22, 5679-5689.

Innes, R. W. (2004). Guarding the Goods. New Insights into the Central Alarm System of Plants. Plant Physiol 135, 695-701. Jakobek, J. L., Smith, J. A., and Lindgren, P. B. (1993). Suppression of bean defense responses by Pseudomonas syringae. Plant Cell 5, 57-63.

Jamir, Y., Guo, M., Oh, H. S., Petnicki-Ocwieja, T., Chen, S., Tang, X., Dickman, M. B., Collmer, A., and Alfano, J. R. (2004). Identification of Pseudomonas syringae type III effectors that can suppress programmed cell death in plants and yeast. Plant J 37, 554-565.

Kim, M.-G., da Cunha, L., Belkhadir, Y., DebRoy, S., Dangl, J. L., and Mackey, D. (2005). Two Pseudomonas syringae type III effectors inhibit RIN4-regulated basal defense in Arabidopsis. Cell 121, 749-759.

Kitigawa, K., Skowyra, D., Elledge, S. J., Harper, J. W., and Hieter, P. (1999). SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of th eSCF ubiquitin complex. Molec Cell 4, 21-33.

Kuang, H., Woo, S. S., Meyers, B. C., Nevo, E., and Michelmore, R. W. (2004). Multiple genetic processes result in heterogeneous rates of evolution within the major cluster disease resistance genes in lettuce. Plant Cell 16, 2870-2894.

Liu, Y., Burch-Smith, T., Schiff, M., Feng, S., and Dinesh-Kumar, S. P. (2004). Molecular chaperone Hsp90 associates with resistance protein N and its signaling proteins SGT1 and Rar1 to modulate an innate immune response in plants. J Biol Chem 279, 2101-2108.

Liu, Y., Schift, M., Serino, G., Deng, X.-W., and Dinesh-Kumar, S. P. (2002). Role of SCF ubiquitin-ligase and the COP9 signalosome in the N-mediated resistance response to tobacco mosaic virus. Plant Cell 14, 1483-1496.

Lu, R., Malcuit, I., Moffett, P., Ruiz, M. T., Peart, J., Wu, A. J., Rathjen, J. P., Bendahmane, A., Day, L., and Baulcombe, D. C. (2003). High throughput virus-induced gene silencing implicates heat shock protein 90 in plant disease resistance. Embo J 22, 5690-5699.

Mackey, D., Belkhadir, Y., Alonso, J. M., Ecker, J. R., and Dangl, J. L. (2003). Arabidopsis RIN4 is a target of the type III virulence effector AvrRpt2 and modulates RPS2-mediated resistance. Cell 112, 379-389.

Mackey, D., Holt III, B. F., Wiig, A., and Dangl, J. L. (2002). RIN4 interacts with Pseudomonas syringae Type III effector molecules and is required for RPM1-mediated disease resistance in Arabidopsis. Cell 108, 743-754.

Moffett, P., Farnham, G., Peart, J., and Baulcombe, D. C. (2002). Interaction between domains of a plant NBS-LRR protein in disease resistance-related cell death. Embo J 21, 4511-4519.

Navarro, L., Zipfel, C., Rowland, O., Keller, I., Robatzek, S., Boller, T., and Jones, J. D. G. (2004). The Transcriptional Innate Immune Response to flg22. Interplay and Overlap with Avr Gene-Dependent Defense Responses and Bacterial Pathogenesis. Plant Physiol 135, 1113-1128.

Nimchuk, Z., Eulgem, T., Holt, I. B., and Dangl, J. L. (2003). Recognition and response in the plant immune system. Annu Rev Genet 37, 579-609.

Nimchuk, Z., Marois, E., Kjemtrup, S., Leister, R. T., Katagiri, F., and Dangl, J. L. (2000). Eukaryotic fatty acylation drives plasma membrane targeting and enhances function of several Type III effector proteins from Pseudomonas syringae. Cell 101, 353-363.

Nimchuk, Z., Rohmer, L., Chang, J. H., and Dangl, J. L. (2001). Knowing the dancer from the dance: R gene products and their interactions with other proteins from host and pathogen. Curr Opin Plant Biol 4, 288-294.

Peart, J. R., Lui, R., Sadanandom, A., Malcuit, I., Moffett, P., Brice, D. C., Schauser, L., Jaggard, D. A. W., Xiao, S., Coleman, M. J., et al. (2002). Ubiquitin ligase-associated protein SGT1 is required for host and non-host disease resistance in plants. Proc Natl Acad Sci U S A 99, 10865-10869.

Rathjen, J. P., and Moffett, P. (2003). Early signal transduction events in specific plant disease resistance. Curr Opin Plant Biol 6, 300-306. Ritter, C., and Dangl, J. L. (1995). The avrRpm1 gene of Pseudomonas syringae pv. maculicola is required for virulence on Arabidopsis. Mol Plant-Microbe Interact 8, 444-453.

Ron, M., and Avni, A. (2004). The Receptor for the Fungal Elicitor Ethylene-Inducing Xylanase Is a Member of a Resistance-Like Gene Family in Tomato. Plant Cell 16, 1604-1615. Shao, F., Golstein, C., Ade, J., Stoutemyer, M., Dixon, J. E., and Innes, R. W. (2003). Cleavage of Arabidopsis PBS1 by a bacterial type III effector. Science 301, 1230-1233.

Shirasu, K., Lahaye, T., Tan, M. W., Zhou, F., Azevedo, C., and Schulze-Lefert, P. (1999). A novel class of eukaryotic zinc-binding proteins is required for disease resistance signaling in barley and development in C. elegans. Cell 99, 355-366.

Steensgaard, P., Garre, M., Muradore, I., Transidico, P., Nigg, E. A., Kitagawa, K., Earnshaw, W. C., Faretta, M., and Musacchio, A. (2004). Sgt1 is required for human kinetochore assembly. EMBO Rep 5, 626-631.

Takahashi, A., Casais, C., Ichimura, K., and Shirasu, K. (2003). HSP90 interacts with RAR1 and SGT1 and is essential for RPS2-mediated disease resistance in Arabidopsis. Proc Natl Acad Sci U S A. Tao, Y., Xie, Z., Chen, W., Glazebrook, J., Chang, H. S., Han, B., Zhu, T., Zou, G., and Katagiri, F. (2003). Quantitative nature of Arabidopsis responses during compatible and incompatible interactions with the bacterial pathogen Pseudomonas syringae. Plant Cell 15, 317-330.

Tör, M., Gordon, P., Cuzick, A., Eulgem, T., Sinapidou, E., Mert, F., Can, C., Dangl, J. L., and Holub, E. B. (2002). Arabidopsis SGT1b is required for defense signaling conferred by several Downy Mildew (Peronospora parasitica) resistance genes. Plant Cell 14, 993-1003.

Tornero, P., Merritt, P., Sadanandom, A., Shirasu, K., Innes, R. W., and Dangl, J. L. (2002). RAR1 and NDR1 contribute quantitatively to disease resistance in Arabidopsis and their relative contributions are dependent on the R gene assayed. Plant Cell 14, 1005-1015.

van der Biezen, E. A., and Jones, J. D. G. (1998). Plant disease resistance proteins and the "gene-for-gene" concept. Trends Biochem Sci 23, 454-456. Van der Hoorn, R. A., De Wit, P. J., and Joosten, M. H. (2002). Balancing selection favors guarding resistance proteins. Trends Plant Sci 7, 67-71.

Zhao, Y., Thilmony, R., Bender, C. L., Schaller, A., He, S. Y., and Howe, G. A. (2003). Virulence systems of Pseudomonas syringae pv. tomato promote bacterial speck disease in tomato by targeting the jasmonate signaling pathway. Plant J 36, 485-499.

Zipfel, C., Robatzek, S., Navarro, L., Oakeley, E. J., Jones, J. D., Felix, G., and Boller, T. (2004). Bacterial disease resistance in Arabidopsis through flagellin perception. Nature 428, 764-767.