• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of prosciprotein sciencecshl presssubscriptionsetoc alertsthe protein societyjournal home
Protein Sci. Dec 2009; 18(12): 2615–2623.
Published online Oct 20, 2009. doi:  10.1002/pro.274
PMCID: PMC2821279

Structural and functional characterization of a triple mutant form of S100A7 defective for Jab1 binding

Abstract

S100A7 (psoriasin) is a calcium- and zinc-binding protein implicated in breast cancer. We have shown previously that S100A7 enhances survival mechanisms in breast cells through an interaction with c-jun activation domain binding protein 1 (Jab1), and an engineered S100A7 triple mutant (Asp56Gly, Leu78Met, and Gln88Lys—S100A73) ablates Jab1 binding. We extend these results to include defined breast cancer cell lines and demonstrate a disrupted S100A73/Jab1 phenotype is maintained. To establish the basis for the abrogated Jab1 binding, we have recombinantly produced S100A73, demonstrated that it retains the ability to form an exceptionally thermostable dimer, and solved the three dimensional crystal structure to 1.6 Å. Despite being positioned at the dimer interface, the Leu78Met mutation is easily accommodated and contributes to a methionine-rich pocket formed by Met12, Met15, and Met34. In addition to altering the surface charge, the Gln88Lys mutation results in a nearby rotameric shift in Tyr85, leading to a substantially reorganized surface cavity and may influence zinc binding. The final mutation of Asp56 to Gly results in the largest structural perturbation shortening helix IV by one full turn. It is noteworthy that position 56 lies in one of two divergent clusters between S100A7 and the functionally distinct yet highly homologous S100A15. The structure of S100A73 provides a unique perspective from which to characterize the S100A7-Jab1 interaction and better understand the distinct functions between S100A7, and it is closely related paralog S100A15.

Keywords: S100A7, psoriasin, x-ray crystallography, Jab1, zinc, calcium, S100A15

Introduction

S100A7, also known as psoriasin, is a member of the S100 family of small (~12 kDa) calcium-binding proteins. S100 proteins are characterized by two conserved EF-hand motifs responsible for calcium coordination and exhibit 25–65% sequence identity at the amino acid level.1 Genes encoding S100 proteins are found exclusively in vertebrates with more than 20 human genes identified, 17 of which are tightly packaged in the 1q21 locus of the human genome, a region frequently rearranged in cancer.25

S100A7 was originally observed as a highly upregulated protein in lesions of psoriatic skin6 and has since been established as a marker of skin inflammation.7,8 S100A7 is postulated to be a chemotactic factor for leukocytes9,10 by engaging the receptor for advanced glycation end products (RAGE) in a zinc-dependent manner10 and may act as a host-defense protein that selectively kills Gram negative bacteria on the surface of the skin and within the oral cavity.1113 In addition to its involvement in host defense and inflammatory processes, S100A7 is also associated with predominantly squamous cell malignancies from a variety of organ sites, including the breast, skin, and lung and also nonsquamous ovarian cancer.1416 Of these diseases, S100A7 has been most extensively studied in the context of breast cancer. Expression of S100A7 is generally absent in normal breast epithelial cells, whereas the frequency and level of expression increases dramatically in ductal carcinoma in situ, the most common precursor lesion of invasive breast cancers.17,18 Maintenance of S100A7 expression in invasive breast carcinoma is associated with aggressive, high grade, estrogen receptor negative lesions, and poor patient outcome.18,19

In addition to S100A7's ability to interact with a variety of proteins (RAGE,10 RanBPM,20 transglutaminase21 epidermal fatty acid binding protein,22,23), the interaction partner currently most relevant to breast cancer is the multifunctional c-jun activation domain binding protein 1 (Jab1—also known as CSN5 or COPS5). The ubiquitously expressed Jab1 is conserved throughout the eukaryotic domain, including ancient organisms such as Saccharomyces cerevisiae, Candida elegans, and Arabidopsis Thaliana,24 and serves as a critical component of the COP9 signalosome, an eight-subunit protein complex important in the regulation of protein stability via the control of Skp1-Cul1-F-box protein-ubiquitin ligase activity.24 Jab1 also has roles independent of the COP9 complex, including down regulation of the cell cycle inhibitor p27KIP1,25 and has recently been identified as a master regulator promoting the poor-prognosis gene expression pattern in breast cancer known as the “wound-response” signature.26

S100A7 has been shown to interact with Jab1 in yeast-two-hybrid assays through a mechanism dependent on the C-terminal half of S100A7.27 This interaction is also observed in human breast cell lines, from which both native and exogenously expressed S100A7 can be specifically coimmunoprecipitated with endogenous Jab1.27 By analyzing costructures of related S100 proteins with their binding partners (S100B-p53,28 S100A10-annexin II,29 and S100A12-RAGE30), we were able to narrow the Jab1 binding site on S100A7. A short list of 20 residues was identified including Asp56, Leu78, and Gln88 that form part of a putative Jab1 binding motif (Asp-N21-Leu-N9-X, where N represents any amino acid and X a polar residue), defined for the Jab1 binding proteins c-jun and p27KIP1.27,31 Interestingly, 17 of the 20 positions are found on helices III or IV or within the connecting loop region and are in close proximity to Asp56, Leu78, or Gln88. Furthermore, sequence divergence at positions 56 and 88 is very high, suggesting an important role in defining ligand binding specificity of the individual S100 proteins (Fig. (Fig.1).1). Mutation of these three residues in S100A7 (Asp56Gly, Leu78Met, and Gln88Lys—S100A73) abrogates both the S100A7-Jab1 interaction as determined by yeast-two-hybrid (Y2H) assay and coimmunoprecipitation31 and the associated tumor promoting effects ascribed to wild-type S100A7. We have recently extended our initial Y2H screen to include contributions of the individual mutations in S100A73 each of which show a significant effect on Jab1 binding.33 In the absence of biochemical and structural characterization, however, these Y2H results are not easily rationalized and suggest a complex interaction between S100A7 and the larger Jab1.

Figure 1
Ligand binding residues in S100 family members correspond to the Asp56/Leu78/Gln88 region of S100A7. Amino acid sequences of the indicated proteins were aligned with ClustalW32 and shaded according to degree of conservation (black indicates identical ...

It is clear from both in vitro and in vivo studies that S100A7 serves an important role in the progression of breast cancer and that much of its influence may be dependent on a functional interaction with Jab1. To study the basis for this interaction and further interpret our Y2H data, we present a detailed structural characterization of S100A73 lacking the ability to bind Jab1. We also discuss our results in the context of the paralog S100A15 that despite sharing 93% identity with S100A7, displays a divergent functional profile.

Results and Discussion

S100A73 lacks function related to invasiveness

We have reported previously that the most prominent effect of S100A7 expression in MDA-MB-231 breast carcinoma cells is enhanced survival, and the role of the S100A7-Jab1 pathway in this effect has been confirmed with the S100A73 triple mutant (Asp56Gly, Leu78Met, and Gln88Lys).27 We have also shown S100A7 to promote invasiveness in breast cells, but the importance of the Jab1 interaction for this effect is unknown. Therefore, to further characterize the functional significance of the Jab1 binding motif, we have examined the ability of the S100A73 triple mutant to promote migration in an in-vitro scratch assay using parental MDA-MB-231 cells and subclones stably transfected to express wild-type (231-S100A7) or the triple mutant (231-S100A73).27,31 As expected, expression of wild-type S100A7 significantly increased the rate of wound closure, relative to parental control cells [Fig. [Fig.2(A)].2(A)]. In contrast, expression of S100A73 was ineffective in enhancing the rate of cell migration. The difference in relative migration rates between 231-S100A7 and either 231-parental or 231-S100A73 was highly significant (P < 0.0001) [Fig. [Fig.2(B)],2(B)], clearly illustrating that the strategically engineered mutations at positions 56, 78, and 88 of S100A73 produce an important biological phenotype.

Figure 2
S100A73 fails to promote cell migration. Influence of S100A7 and S100A73 on intrinsic migration in MDA-MB-231 cells. Parental MDA-MB-231 cells and clones stably expressing either wild type S100A7 or S100A73 were grown to confluence in replicates of 6 ...

S100A73 forms a stable dimer

As a first step toward determining whether the incorporation of the three engineered mutations adversely affects the intermolecular or intramolecular integrity of the protein, we developed an efficient recombinant protein production system. When compared with a series of globular protein standards, S100A73 elutes as a dimer of approximately 26 kDa from an Sx75 size exclusion column similar to wild-type S100A7 [Fig. [Fig.3(A),3(A), left panel]. Furthermore, there is no evidence of an S100A73 monomer or soluble aggregate. Melting curves monitored by circular dichroism show that S100A73 retains its structure up to 95°C, as does the wild-type S100A7, confirming the three mutations do not adversely affect the integrity of the protein. This result is particularly intriguing in that we are able to further interpret our previous results where we showed impaired binding of S100A73 to Jab1.27 Based on the stability of the S100A73 dimer, the abrogated S100A73/Jab1 interaction is due to selective disruption of the Jab1 binding site on S100A7 rather than global structural rearrangement.

Figure 3
S100A73 forms a stable dimer. A. FPLC trace and associated sodium dodecyl sulfate polyacrylamide gel electrophoresis showing the stable S100A73 dimer. B. Ribbon diagram of the 1.6 Å resolution S100A73 monomer (blue) and crystallographically generated ...

Overall structure of S100A73

To fully define the structural implications associated with the S100A73 triple mutant, we solved the crystal structure of S100A73 to a resolution of 1.6 Å. S100A73 crystallized with one monomer in the asymmetric unit [Fig. [Fig.3(B),3(B), left panel] of the tetragonal unit cell with the second molecule of the physiological dimer generated by the crystallographic twofold axis [Fig. [Fig.3(B),3(B), right panel]. The overall helical architecture of S100A73 is conserved with wild-type S100A734,35 with an overall root mean square deviation of 0.79 Å over 90 Cα atoms. Of the five core helices, I and V form the dimer interface resulting in a buried surface area of 3250 Å2 [Fig. [Fig.3(B)].3(B)]. Each S100A7 monomer coordinates one tightly bound calcium ion (B-factor - 10.43 Å2) in a canonical EF-hand motif incorporating the C-terminal end of helix IV, the connected inter helical loop, and the N-terminal portion of helix V. In addition, two partially occupied zinc ions are bound at the homodimer interface with two histidine ligands derived from the C-terminal end of helix V from one monomer with the remaining histidine and aspartate ligand provided by the C-terminal end of helix I of the second monomer. Final data collection and refinement statistics are presented in Table TableII.

Table I
Data Collection and Refinement Statistics

While none of the three mutations cause major structural rearrangements, a detailed analysis reveals a likely binding site for Jab1. The mutation of Asp56 to Gly results in a localized structural perturbation where a stretch of amino acids extending from Asn52 to Lys61 and incorporating helix IV is displaced approximately 0.9 Å relative to native S100A7 [Fig. [Fig.4(A)].4(A)]. The structural shift is due to a truncation of helix IV by one full turn caused by the incorporation of glycine. Despite the reorganized secondary structure, the positions of nearby side-chains are highly conserved between the wild-type and mutant forms [Fig. [Fig.4(A)].4(A)]. Because of the orientation of the Asp56 side-chain in native S100A7 where the polar head group is directed away from solvent, the mutation to Gly in S100A73 does not significantly alter the localized surface charge of the protein. The structural perturbation at position 56 correlates with our Y2H data that suggests a principal role for Asp56 in mediating Jab1 binding.33

Figure 4
Structural effect of the three mutations in S100A73. In each figure, the blue surface represents the S100A73 monomer with the physiological dimer partner shown in grey. Each mutation is colored on the monomer surface (Asp56 - red, Lys88 - blue and Met ...

The substitution of one surface exposed, extended polar residue (Gln88) for another (Lys) results in an unexpected structural reorganization of a nearby tyrosine (Tyr85) [Fig. [Fig.4(B)].4(B)]. The longer side chain of Lys88 forces a rotameric shift of Tyr85 such that the terminal OH group is displaced by 8 Å. The mutation to Lys at position 88 and the repositioned side-chain of Tyr85 combine to reduce the size of a surface cavity observed in native S100A7 by nearly half while presenting an electrostatically distinct surface. Intriguingly, Gln88 is framed by zinc ligands His86 and His90, which lie on the opposite side of helix V and as a result mutations at position 88 may influence zinc binding. Despite the structural and chemical reorganization associated with the Gln88Lys mutation, a relatively small effect is observed in Jab1 binding.33 One possible explanation is that Gln88 participates peripherally in Jab1 binding or is indirectly involved through contributing to the stability of the nearby zinc site. In the latter case, destabilizing effects may only be observed with reduced zinc concentrations such as those present in a cell.

The mutation of Leu to Met at position 78, while structurally conservative, was expected to affect dimer stability due to its position in the core of the dimer interface. Of the three mutations characterized here, however, Leu78Met shows the least structural reorganization with both the surrounding side chains and the spatial positioning of the symmetry-related helices being structurally invariant [Fig. [Fig.4(C)].4(C)]. Consistent with these observations are well-ordered electron density and low B-factors for the Met78 side-chain. One particularly interesting feature of the Leu78Met mutant is the resulting methionine rich pocket formed at the dimer interface where the Sδ atoms of four methionine residues from one monomer (Met12, Met15, Met34, and Met78) are positioned within 4.4 Å of each other. Additional emphasis is placed on this pocket based in our recent costructure of S100A7 with 2-anilinonapthalene-6-sulfonic acid that reveals an unexpected reorganization of the Met12 side chain, resulting in a deep small molecule-binding cavity immediately adjacent to Leu78.33 Additional studies are required to clearly establish the relevance of this pocket to Jab1 binding, but because both individual Leu78Met and Asp56Gly mutants result in significant disruption of Jab1 binding, we are continuing to pursue both regions for small molecule design targeted at disrupting the S100A7/Jab1 interaction.

Functional implications: comparing S100A7 and S100A15

The biological and structural effects of the Asp56Gly, Leu78Met, and Gln88Lys mutations can be further interpreted in the context of the functional differences between S100A7, and its closely related paralog S100A15 with which it shares 93% identity [Fig. (5)]. Although S100A15 and S100A7 share functions in the skin related to inflammation, they have been shown to be functionally distinct, at least in their extracellular actions.10 Furthermore, the three amino acid “Jab1 binding” motif is absent in human S100A15.36 Structural mapping of the seven divergent amino acids of S100A15 onto the backbone of S100A7 reveals two spatially distinct regions [Fig. (5)]. These sites may be crucial in defining the functional differences between S100A7 and S100A15 (Fig. (Fig.4).4). The first region is a putative protein interaction “hotspot” that includes Asp56 (Thr—S100A15 residues displayed in brackets) and closely flanking Thr51(Ile) and Asn52(His). Asp56 is replaced with glycine in S100A73, where it results in a backbone rearrangement and truncation of helix IV by one full turn and is sufficient to abrogate Jab1 binding in the Y2H assay.33 The second divergent cluster between S100A7 and S100A15 is the zinc-binding region that includes Arg21(Gly), Asp24(Gly), Asp27 (Glu), and Thr83(Ala) (Fig. (Fig.5).5). The effect of zinc on the S100A7/Jab1 interaction is currently unknown, but perturbation of S100A7 zinc binding is known to have significant functional effects in binding to the RAGE receptor.10

Figure 5
Structural and functional implications of S100A7 and S100A15. S100A15 shares 93% identity with S100A7 with the seven mutations clustered into two spatial groups. The S100A15 mutations are mapped to the backbone of S100A7 (grey) as cyan surfaces with the ...

Conclusions

The S100A7-Jab1 interaction may be a critical factor in breast cancer progression. We present a detailed structural characterization of S100A73, a triple mutant form unable to bind Jab1 and an important resource in the study of the S1000A7-Jab1 interaction in breast cancer. Based on the exceptional thermostability of the S100A73 dimer, we conclude the three strategically designed mutations play a role in specifically disrupting the S100A7-Jab1 binding interaction rather than simply causing global structural reorganization. Structural analysis reveals a direct correlation between the localized rearrangement associated with the Asp56Gly mutation and the most significant abrogative effect on Jab1 binding.33 Intriguingly, S100A15 encodes a Thr at position 56 that forms one of the divergent clusters that may be responsible for the functional differences between S100A7 and S100A15. The contributions of Gln88 and Leu78 to Jab1 binding are more difficult to assess although the intriguing possibility exists that substitutions at position 88 may influence zinc binding.

Materials and Methods

In vitro migration assay

MDA-MB-231 breast carcinoma cells were maintained in Dulbecco's modified eagle medium supplemented with 10% fetal bovine serum, under standard conditions. The generation of subclones over expressing wild-type S100A7 or the Jab1-binding domain mutant form (S100A73) has been described previously.27,31 For in vitro migration assays, the three cell lines (231-parental, 231-S100A7, and 231-S100A73) were grown to confluence in multiwell culture dishes (Corning). Cell monolayers were then scratched with a sterile p200 pipette tip to generate wounds, media was changed to remove floating cells, and images of wounds were captured at 100× magnification (0 hour time-point) with a QICAM (Qimaging) camera mounted to an Axiovert 40 CFL light microscope (Zeiss). A second set of images was captured after 20 hours. Wound widths at the two time-points were measured using ImageJ. Relative migration distances were compared with GraphPad Prism 5.0 using Student's t test. Assays were performed three times, each with six replicate wounds.

Production and purification of soluble S100A7

The triple mutant (Asp56Gly, Leu78Met and Gln88Lys) construct of human S100A7 (S100A73) was generated using polymerase chain reaction mutagenesis as described previously27 and subcloned into pET32a (Novagen). Recombinant production of S100A73 was carried out in Escherichia coli Rosetta-Gammi B (Invitrogen, Carlsbad, CA) grown in Overnight Express™ Instant TB Medium (Novagen) supplemented with 50 μg/mL ampicillin and 30μg/mL chloramphenicol (Sigma, Canada). Cells were grown at 37°C and harvested the following morning. The harvested cells were resuspended in 20 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer pH 8, 20 mM imidazole and 1M NaCl (buffer A) and lysed with a French press. The insoluble material was removed be centrifugation, and the supernatant was applied directly to a HisTrap FF 5mL column (Qiagen) equilibrated with buffer A. S100A73 fractions were eluted with an increasing concentration of imidazole, analyzed with sodium dodecyl sulfate polyacrylamide gel electrophoresis, pooled based on purity, and concentrated. The hexa-histidine tag was proteolytically removed with thrombin (Novagen, USA) and the protein purified on a superdex™ Sx75 gel filtration column (Amersham Biosciences) equilibrated with 20 mM HEPES and 150 mM NaCl.

Crystallization, data collection, processing, and structure solution

S100A73 was concentrated to 81.6 mg/mL and crystallized using the sitting drop vapor diffusion method at 18°C in 0.05M ammonium sulfate, 0.05M Bis-Tris pH 6.5 and 30% v/v pentaerythritol ethoxylate (15/4 EO/OH). Diffraction data were collected on a Rigaku R-axis IV++ area detector coupled to an MM-002 x-ray generator with Osmic “blue” optics and an Oxford Cryostream 700. Diffraction data to 1.6 Å were processed using Crystal Clear software with d*trek.37 Data collection and refinement statistics are presented in Table TableII.

All refinement steps were carried out using the CCP4 suite of programs.38 Phases were obtained by molecular replacement using MOLREP39 with the monomeric form of native S100A7 (PDBID 2PSR) used as the search model. Solvent atoms were selected using COOT40 and the overall structure refined with REFMAC.39 Stereo-chemical analysis of the refined S100A73 structure was performed with PROCHECK and SFCHECK in CCP438 with the Ramachandran plot showing excellent stereochemistry with 97.9% of the residues in the favored conformation and the remaining 2.1% in the allowed region. Overall 5% of the reflections were set aside for calculation of Rfree.

Protein Data Bank accession code

The coordinate and structure factor files for triple mutant S100A73 have been deposited to the Protein Data Bank with accession code 2wnd.

Acknowledgments

MJB is a Canadian Institutes of Health Research New Investigator and MJB and FH are Michael Smith Foundation for Health Research (MSFHR) scholars.

Glossary

Abbreviations:

Jab1
c-jun activation domain binding protein 1
RAGE
receptor for advanced glycation end products.

References

1. Santamaria–Kisiel L, Rintala-Dempsey AC, Shaw GS. Calcium-dependent and -independent interactions of the S100 protein family. Biochem J. 2006;396:201–214. [PMC free article] [PubMed]
2. Engelkamp D, Schafer BW, Mattei MG, Erne P, Heizmann CW. Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. Proc Natl Acad Sci USA. 1993;90:6547–6551. [PMC free article] [PubMed]
3. Schafer BW, Wicki R, Engelkamp D, Mattei MG, Heizmann CW. Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium–binding protein family. Genomics. 1995;25:638–643. [PubMed]
4. Marenholz I, Heizmann CW, Fritz G. S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature) Biochem Biophys Res Commun. 2004;322:1111–1122. [PubMed]
5. Sturchler E, Cox JA, Durussel I, Weibel M, Heizmann CW. S100A16, a novel calcium–binding protein of the EF-hand superfamily. J Biol Chem. 2006;281:38905–38917. [PubMed]
6. Madsen P, Rasmussen HH, Leffers H, Honore B, Dejgaard K, Olsen E, Kiil J, Walbum E, Andersen AH, Basse B, et al. Molecular cloning, occurrence, and expression of a novel partially secreted protein “psoriasin” that is highly up-regulated in psoriatic skin. J Invest Dermatol. 1991;97:701–712. [PubMed]
7. Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, Morel F. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol. 2005;174:3695–3702. [PubMed]
8. Boniface K, Diveu C, Morel F, Pedretti N, Froger J, Ravon E, Garcia M, Venereau E, Preisser L, Guignouard E, Guillet G, Dagregorio G, Pène J, Moles JP, Yssel H, Chevalier S, Bernard FX, Gascan H, Lecron JC. Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation. J Immunol. 2007;178:4615–4622. [PubMed]
9. Jinquan T, Vorum H, Larsen CG, Madsen P, Rasmussen HH, Gesser B, Etzerodt M, Honore B, Celis JE, Thestrup-Pedersen K. Psoriasa novel chemotactic protein. J Invest Dermatol. 1996;107:5–10. [PubMed]
10. Wolf R, Howard OM, Dong HF, Voscopoulos C, Boeshans K, Winston J, Divi R, Gunsior M, Goldsmith P, Ahvazi B, Chavakis T, Oppenheim JJ, Yuspa SH. Chemotactic activity of S100A7 (psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15. J Immunol. 2008;181:1499–1506. [PMC free article] [PubMed]
11. Glaser R, Harder J, Lange H, Bartels J, Christophers E, Schroder JM. Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol. 2005;6:57–64. [PubMed]
12. Lee KC, Eckert RL. S100A7 (psoriasin)—mechanism of antibacterial action in wounds. J Invest Dermatol. 2007;127:945–957. [PubMed]
13. Meyer JE, Harder J, Sipos B, Maune S, Kloppel G, Bartels J, Schroder JM, Glaser R. Psoriasin (S100A7) is a principal antimicrobial peptide of the human tongue. Mucosal Immunol. 2008;1:239–243. [PubMed]
14. Alowami S, Qing G, Emberley E, Snell L, Watson PH. Psoriasin (S100A7) expression is altered during skin tumorigenesis. BMC Dermatol. 2003:3–1. [PMC free article] [PubMed]
15. Emberley ED, Murphy LC, Watson PH. S100A7 and the progression of breast cancer. Breast Cancer Res. 2004b;6:153–159. [PMC free article] [PubMed]
16. Gagnon A, Kim JH, Schorge JO, Ye B, Liu B, Hasselblatt K, Welch WR, Bandera CA, Mok SC. Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients. Clin Cancer Res. 2008;14:764–771. [PubMed]
17. Leygue E, Snell L, Hiller T, Dotzlaw H, Hole K, Murphy LC, Watson PH. Differential expression of psoriasin messenger RNA between in situ and invasive human breast carcinoma. Cancer Res. 1996;56:4606–4609. [PubMed]
18. Emberley ED, Alowami S, Snell L, Murphy LC, Watson PH. S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast. Breast Cancer Res. 2004a;6:R308–R315. [PMC free article] [PubMed]
19. Emberley ED, Niu Y, Njue C, Kliewer EV, Murphy LC, Watson PH. Psoriasin (S100A7) expression is associated with poor outcome in estrogen receptor–negative invasive breast cancer. Clin Cancer Res. 2003b;9:2627–2631. [PubMed]
20. Emberley ED, Gietz RD, Campbell JD, HayGlass KT, Murphy LC, Watson PH. RanBPM interacts with psoriasin in vitro and their expression correlates with specific clinical features in vivo in breast cancer. BMC Cancer. 2002;2:28. [PMC free article] [PubMed]
21. Ruse M, Lambert A, Robinson N, Ryan D, Shon KJ, Eckert RL. S100A7, S100A10, and S100A11 are transglutaminase substrates. Biochemistry. 2001;40:3167–3173. [PubMed]
22. Hagens G, Masouye I, Augsburger E, Hotz R, Saurat JH, Siegenthaler G. Calcium-binding protein S100A7 and epidermal-type fatty acid-binding protein are associated in the cytosol of human keratinocytes. Biochem J. 1999;339:419–427. [PMC free article] [PubMed]
23. Ruse M, Broome AM, Eckert RL. S100A7 (psoriasin) interacts with epidermal fatty acid binding protein and localizes in focal adhesion–like structures in cultured keratinocytes. J Invest Dermatol. 2003;121:132–141. [PubMed]
24. Cope GA, Deshaies RJ. COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell. 2003;114:663–671. [PubMed]
25. Tomoda K, Kubota Y, Arata Y, Mori S, Maeda M, Tanaka T, Yoshida M, Yoneda–Kato N, Kato JY. The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. J Biol Chem. 2002;277:2302–2310. [PubMed]
26. Adler AS, Lin M, Horlings H, Nuyten DS, van de Vijver MJ, Chang HY. Genetic regulators of large-scale transcriptional signatures in cancer. Nat Genet. 2006;38:421–430. [PMC free article] [PubMed]
27. Emberley ED, Niu Y, Leygue E, Tomes L, Gietz RD, Murphy LC, Watson PH. Psoriasin interacts with Jab1 and influences breast cancer progression. Cancer Res. 2003a;63:1954–1961. [PubMed]
28. Rustandi RR, Baldisseri DM, Weber DJ. Structure of the negative regulatory domain of p53 bound to S100B(betabeta) Nat Struct Biol. 2000;7:570–574. [PubMed]
29. Rety S, Sopkova J, Renouard M, Osterloh D, Gerke V, Tabaries S, Russo–Marie F, Lewit-Bentley A. The crystal structure of a complex of p11 with the annexin II N-terminal peptide. Nat Struct Biol. 1999;6:89–95. [PubMed]
30. Xie J, Burz DS, He W, Bronstein IB, Lednev I, Shekhtman A. Hexameric calgranulin C (S100A12) binds to the receptor for advanced glycated end products (RAGE) using symmetric hydrophobic target-binding patches. J Biol Chem. 2007;282:4218–4231. [PubMed]
31. Emberley ED, Niu Y, Curtis L, Troup S, Mandal SK, Myers JN, Gibson SB, Murphy LC, Watson PH. The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer. Cancer Res. 2005;65:5696–5702. [PubMed]
32. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position–specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673–4680. [PMC free article] [PubMed]
33. León R, Murray JI, Cragg G, Farnell B, West NR, Pace TCS, Watson PH, Bohne C, Boulanger MJ, Hof F. Identification and characterization of binding sites on S100A7, a participant in cancer and inflammation. Biochemistry. 2009;48:10591–10600. [PubMed]
34. Brodersen DE, Etzerodt M, Madsen P, Celis JE, Thogersen HC, Nyborg J, Kjeldgaard M. EF-hands at atomic resolution: the structure of human psoriasin (S100A7) solved by MAD phasing. Structure. 1998;6:477–489. [PubMed]
35. Heizmann CW, Cox JA. New perspectives on S100 proteins: a multi–functional Ca(2+)-, Zn(2+)- and Cu(2+)-binding protein family. Biometals. 1998;11:383–397. [PubMed]
36. Webb M, Emberley ED, Lizardo M, Alowami S, Qing G, Alfia'ar A, Snell–Curtis LJ, Niu Y, Civetta A, Myal Y, Shiu R, Murphy L, Watson P. Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis. BMC Cancer. 2005;5:17. [PMC free article] [PubMed]
37. Pflugrath J. The finer things in X–ray diffraction data collection. Acta Crystallog sect D. 1999;55:1718–1725. [PubMed]
38. Collaborative Computational Project Number 4. The CCP4 Suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr. 1994;50:760–763. [PubMed]
39. Murshudov GN, Vagin AA, Dodson EJ. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallog sect D. 1997;53:240–255. [PubMed]
40. Emsley P, Cowtan K. Coot: model–building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004;60:2126–2132. [PubMed]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...