S100 proteins as therapeutic targets

Bresnick, Anne R.

doi:10.1007/s12551-018-0471-y

Cited by 71 publications

(84 citation statements)

References 185 publications

(234 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The 20 S100 paralogs, whose interactions were studied here, represent almost the complete human S100ome [13]. It is a Chordata-specific, evolutionary young protein family, and despite the fact that they exhibit moderate sequence similarity, they are structurally very similar owing to their small size (~100 residues) and conserved fold (including two consecutive EF hand motifs) ( Fig S16.).…”

Section: Specificity Map Of the S100omementioning

confidence: 99%

“…S100s are associated with several disease conditions, such as cardiomyopathies, cancer, inflammatory and neurodegenerative diseases, in which overexpression of S100 proteins can be observed in the affected cells [10][11][12]. Due to this reason, they are emerging bio-markers and also promising therapeutic targets [13]. Despite their growing importance, the literature still lacks their comprehensive and systematic analysis, which would be essential for developing rational strategies for drug development.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High throughput competitive fluorescence polarization assay reveals functional redundancy in the S100 protein family

Simon

Gógl

Ecsédi

et al. 2019

Preprint

View full text Add to dashboard Cite

The calcium-binding, vertebrate-specific S100 protein family consists of 20 paralogs in humans (referred as the S100ome), with several clinically important members. To assess their interactome, high-throughput, systematic analysis is indispensable, which allows one to get not only qualitative but quantitative insight into their protein-protein interactions (PPIs). We have chosen an unbiased assay, fluorescence polarization (FP) that revealed a partial functional redundancy when the complete S100ome (n=20) was tested against numerous model partners (n=13). Based on their specificity, the S100ome can be grouped into two distinct classes: promiscuous and orphan. In the first group, members bound to several ligands (>4-5) with comparable high affinity, while in the second one, the paralogs bound only one partner weakly, or no ligand was identified (orphan). Our results demonstrate that in vitro FP assays are highly suitable for quantitative ligand binding studies of selected protein families. Moreover, we provide evidence that PPI-based phenotypic characterization can complement the information obtained from the sequence-based phylogenetic analysis of the S100ome, an evolutionary young protein family. Author summaryFunctional similarity among a protein family can be essential in order to understand proteomic data, to find biomarkers, or in inhibitor design. Proteins with similar functions can compensate the loss-offunction of the others, their expression can co-vary under pathological conditions, and simultaneous targeting can lead to better results in the clinics. To investigate this property one can use sequencebased approaches. However, this path can be difficult. In the case of the vertebrate specific, evolutionary young, S100 family, phylogenetic approaches lead to ambiguous results. To overcome this problem, we applied a high-throughput biochemical approach to experimentally measure the binding affinities of a large number of S100 interactions. We performed unbiased fluorescence polarization assay, involving the complete human S100ome (20 paralogs) and 13 known interaction partners. We used this measured 20x13 (260) protein-protein interaction array to reveal the functional relationships within the family. Our work provide a general framework for studies focusing on phenotype-based domain classification.

show abstract

Section: Specificity Map Of the S100omementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High throughput competitive fluorescence polarization assay reveals functional redundancy in the S100 protein family

Simon

Gógl

Ecsédi

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…S100A10 could be an excellent target for cancer treatment, because mouse models suggest that genetic deletion has minimal effects on normal physiology. Different therapeutic strategies have been used to target S100A10, including peptides, neutralizing antibodies, small molecule inhibitors, and all‐trans retinoic acid (ATRA) . An ANXA2 peptide which interferes with ANXA2‐S100A10 complex formation prevents binding of prostate cancer cells and multiple myeloma cells to osteoblasts .…”

Section: Targeting S100a10 For Cancer Therapymentioning

confidence: 99%

“…S100A10 antibodies are effective in reducing leukemia cell homing to the bone marrow in vivo . A number of small molecules that inhibit the formation of the complex have been identified . One of these inhibitors, 5‐benzyl‐4‐methyl‐2‐(toluene‐4‐sulfonylamino)‐thiophene‐3‐carbocylic acid amide, has been shown to inhibit the adhesion of leukemic cells to osteoblasts in vivo …”

Section: Targeting S100a10 For Cancer Therapymentioning

confidence: 99%

Multiple functions of S100A10, an important cancer promoter

Saiki

Horii

2019

Pathology International

View full text Add to dashboard Cite

The S100 group of calcium binding proteins is composed of 21 members that exhibit tissue/cell specific expressions. These S100 proteins bind a diverse range of targets and regulate multiple cellular processes, including proliferation, migration and differentiation. S100A10, also known as p11, binds mainly to annexin A2 and mediates the conversion of plasminogen to an active protease, plasmin. Higher S100A10 expression has been reported to link to worse outcome and/or chemoresistance in a number of cancer types in lung, breast, ovary, pancreas, gall bladder and colorectum and leukemia although some discrepancy was reported. In this review, we focused on the roles of the S100A10 in cancer. We summarized its biological functions, role in cancer progression, prognostic value and targeting of S100A10 for cancer therapy.

show abstract

“…Moreover, the pathogenetic involvement of these molecules qualifies them as relevant drug targets or therapeutics as well. Indeed, accumulating preclinical data have encouraged envisaging DAMPs as therapeutic targets for inhibition [5,[12][13][14][15][16][17] and administration of SAMPs as candidate drugs [5,[18][19][20][21][22][23][24][25][26][27] for treating acute or chronic inflammatory disorders. On the other hand, DAMPs may also be…”

Section: Introductionmentioning

confidence: 99%

Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution

Land

2020

Mol Diagn Ther

View full text Add to dashboard Cite

This opinion article discusses the increasing attention paid to the role of activating damage-associated molecular patterns (DAMPs) in initiation of inflammatory diseases and suppressing/inhibiting DAMPs (SAMPs) in resolution of inflammatory diseases and, consequently, to the future roles of these novel biomarkers as therapeutic targets and therapeutics. Since controlled production of DAMPs and SAMPs is needed to achieve full homeostatic restoration and repair from tissue injury, only their pathological, not their homeostatic, concentrations should be therapeutically tackled. Therefore, distinct caveats are proposed regarding choosing DAMPs and SAMPs for therapeutic purposes. For example, we discuss the need to a priori identify and define a context-dependent "homeostatic DAMP:SAMP ratio" in each case and a "homeostatic window" of DAMP and SAMP concentrations to guarantee a safe treatment modality to patients. Finally, a few clinical examples of how DAMPs and SAMPs might be used as therapeutic targets or therapeutics in the future are discussed, including inhibition of DAMPs in hyperinflammatory processes (e.g., systemic inflammatory response syndrome, as currently observed in , administration of SAMPs in chronic inflammatory diseases, inhibition of SAMPs in hyperresolving processes (e.g., compensatory antiinflammatory response syndrome), and administration/induction of DAMPs in vaccination procedures and anti-cancer therapy.

show abstract

S100 proteins as therapeutic targets

Cited by 71 publications

References 185 publications

High throughput competitive fluorescence polarization assay reveals functional redundancy in the S100 protein family

High throughput competitive fluorescence polarization assay reveals functional redundancy in the S100 protein family

Multiple functions of S100A10, an important cancer promoter

Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution

Contact Info

Product

Resources

About