Short Toxin-like Proteins Attack the Defense Line of  Innate Immunity

Tirosh, Yitshak; Ofer, Dan; Eliyahu, Tsiona; Linial, Michal

doi:10.3390/toxins5071314

Cited by 15 publications

(9 citation statements)

References 58 publications

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“…The uPAR signaling is responsible for initiating invasion and metastasis via the activation of the plasminogen activator/plasmin cascade in breast cancers and play a role in stimulating the RAS/ERK pathway to control invasion in cancer cells [ 148 ]. The LU domain has been predicted to play a role in cancer diagnosis and malfunction of immune system [ 149 ]. It is plausible that all Ly6 family of genes may have common mechanism in tumorigenesis and their role in poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome

et al. 2016

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Stem cell antigen-1 (Sca-1) is used to isolate and characterize tumor initiating cell populations from tumors of various murine models [1]. Sca-1 induced disruption of TGF-β signaling is required in vivo tumorigenesis in breast cancer models [2, 3-5]. The role of human Ly6 gene family is only beginning to be appreciated in recent literature [6-9]. To study the significance of Ly6 gene family members, we have visualized one hundred thirty gene expression omnibus (GEO) dataset using Oncomine (Invitrogen) and Georgetown Database of Cancer (G-DOC). This analysis showed that four different members Ly6D, Ly6E, Ly6H or Ly6K have increased gene expressed in bladder, brain and CNS, breast, colorectal, cervical, ovarian, lung, head and neck, pancreatic and prostate cancer than their normal counter part tissues. Increased expression of Ly6D, Ly6E, Ly6H or Ly6K was observed in sub-set of cancer type. The increased expression of Ly6D, Ly6E, Ly6H and Ly6K was found to be associated with poor outcome in ovarian, colorectal, gastric, breast, lung, bladder or brain and CNS as observed by KM plotter and PROGgeneV2 platform. The remarkable findings of increased expression of Ly6 family members and its positive correlation with poor outcome on patient survival in multiple cancer type indicate that Ly6 family members Ly6D, Ly6E, Ly6K and Ly6H will be an important targets in clinical practice as marker of poor prognosis and for developing novel therapeutics in multiple cancer type.

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Section: Discussionmentioning

confidence: 99%

Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome

et al. 2016

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“…The importance of Ly6 proteins is underscored by their implication in diseases such as Mal de Meleda [ 21 – 23 ]; in nervous system functions such as synaptic transmission, visual plasticity, anxiety, and sleep [ 7 , 14 , 24 , 25 ]; and in immune and stem cell functions [ 16 , 23 , 26 – 32 ]. In some of these cases individual Ly6 proteins have been shown to exert their effects through antagonism of nAChRs, but the mechanisms underlying these effects and the structural motifs that are involved have not been thoroughly investigated.…”

Section: Discussionmentioning

confidence: 99%

Structural Analysis and Deletion Mutagenesis Define Regions of QUIVER/SLEEPLESS that Are Responsible for Interactions with Shaker-Type Potassium Channels and Nicotinic Acetylcholine Receptors

Liu

Joiner

2016

PLoS ONE

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Ly6 proteins are endogenous prototoxins found in most animals. They show striking structural and functional parallels to snake α-neurotoxins, including regulation of ion channels and cholinergic signaling. However, the structural contributions of Ly6 proteins to regulation of effector molecules is poorly understood. This question is particularly relevant to the Ly6 protein QUIVER/SLEEPLESS (QVR/SSS), which has previously been shown to suppress excitability and synaptic transmission by upregulating potassium (K) channels and downregulating nicotinic acetylcholine receptors (nAChRs) in wake-promoting neurons to facilitate sleep in Drosophila. Using deletion mutagenesis, co-immunoprecipitations, ion flux assays, surface labeling and confocal microscopy, we demonstrate that only loop 2 is required for many of the previously described properties of SSS in transfected cells, including interactions with K channels and nAChRs. Collectively our data suggest that QVR/SSS, and by extension perhaps other Ly6 proteins, target effector molecules using limited protein motifs. Mapping these motifs may be useful in rational design of drugs that mimic or suppress Ly6-effector interactions to modulate nervous system function.

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“…ClanTox is species independent, as opposed to ConoDictor and ConoSorter, and can be used to identify toxin-like sequences. For example, ClanTox was used to discover toxin-like proteins in mammalian transcriptomes [ 79 ], and some of the identified peptides are modulators of cell signaling acting at nicotinic acetylcholine receptors using a three-finger snake toxin fold [ 80 , 81 ]. On the basis of convergent evolution of toxins in different phila, Starcevic et al identified sequences motifs that seem to be specifically used by toxins [ 82 ].…”

Section: Discovery Of Toxins From Venom Gland Transcriptomesmentioning

confidence: 99%

Bioinformatics-Aided Venomics

Kaas

Craik

2015

Toxins

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Venomics is a modern approach that combines transcriptomics and proteomics to explore the toxin content of venoms. This review will give an overview of computational approaches that have been created to classify and consolidate venomics data, as well as algorithms that have helped discovery and analysis of toxin nucleic acid and protein sequences, toxin three-dimensional structures and toxin functions. Bioinformatics is used to tackle specific challenges associated with the identification and annotations of toxins. Recognizing toxin transcript sequences among second generation sequencing data cannot rely only on basic sequence similarity because toxins are highly divergent. Mass spectrometry sequencing of mature toxins is challenging because toxins can display a large number of post-translational modifications. Identifying the mature toxin region in toxin precursor sequences requires the prediction of the cleavage sites of proprotein convertases, most of which are unknown or not well characterized. Tracing the evolutionary relationships between toxins should consider specific mechanisms of rapid evolution as well as interactions between predatory animals and prey. Rapidly determining the activity of toxins is the main bottleneck in venomics discovery, but some recent bioinformatics and molecular modeling approaches give hope that accurate predictions of toxin specificity could be made in the near future.

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Short Toxin-like Proteins Attack the Defense Line of Innate Immunity

Cited by 15 publications

References 58 publications

Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome

Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome

Structural Analysis and Deletion Mutagenesis Define Regions of QUIVER/SLEEPLESS that Are Responsible for Interactions with Shaker-Type Potassium Channels and Nicotinic Acetylcholine Receptors

Bioinformatics-Aided Venomics

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