2f373d84a90b0ec6bd43479d7d23766f pmc_9857295.pdf 7c6f01342b13f3579e94d0129cac98e2e392a305 pmc_9857295.pdf e23e200c09a31747706fe9cbbdad0bfc5808e4d1499f44ee1faceca1bc5a6efe pmc_9857295.pdf Title: Role of Moonlighting Proteins in Disease: Analyzing the Contribution of Canonical and Moonlighting Functions in Disease Progression Subject: The term moonlighting proteins refers to those proteins that present alternative functions performed by a single polypeptide chain acquired throughout evolution (called canonical and moonlighting, respectively). Over 78% of moonlighting proteins are involved in human diseases, 48% are targeted by current drugs, and over 25% of them are involved in the virulence of pathogenic microorganisms. These facts encouraged us to study the link between the functions of moonlighting proteins and disease. We found a large number of moonlighting functions activated by pathological conditions that are highly involved in disease development and progression. The factors that activate some moonlighting functions take place only in pathological conditions, such as specific cellular translocations or changes in protein structure. Some moonlighting functions are involved in disease promotion while others are involved in curbing it. The disease-impairing moonlighting functions attempt to restore the homeostasis, or to reduce the damage linked to the imbalance caused by the disease. The disease-promoting moonlighting functions primarily involve the immune system, mesenchyme cross-talk, or excessive tissue proliferation. We often find moonlighting functions linked to the canonical function in a pathological context. Moonlighting functions are especially coordinated in inflammation and cancer. Wound healing and epithelial to mesenchymal transition are very representative. They involve multiple moonlighting proteins with a different role in each phase of the process, contributing to the current-phase phenotype or promoting a phase switch, mitigating the damage or intensifying the remodeling. All of this implies a new level of complexity in the study of pathology genesis, progression, and treatment. The specific protein function involved in a patient’s progress or that is affected by a drug must be elucidated for the correct treatment of diseases. Keywords: moonlighting proteins; wound-healing; cancer wound-healing; stress; inflammation; stem cells; proliferation; fibrosis Author: Mario Huerta, Luis Franco-Serrano, Isaac Amela, Josep Antoni Perez-Pons, Jaume Piñol, Angel Mozo-Villarías, Enrique Querol and Juan Cedano Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jan 5 12:11:03 2023 CET ModDate: Thu Jan 5 13:32:04 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1008599 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QCJOMF+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 RGLSEP+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 DRWWRZ+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 23 0 AHRQMW+VnURWPalladioL Type 1 Custom 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Identity-H yes yes yes 158 0 KNLAFD+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 164 0 KNLAGE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 170 0 KNLAHE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 176 0 KNLAHF+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 179 0 KNLAIG+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 182 0 CRUZTT+VnURWPalladioL-Italic Type 1 Custom yes yes no 238 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-11-11 02:31:48 CET RepresentationInformation: pmc_9857295.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-02-09 02:16:03 CET Size: 1008599 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 745 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Children: Item: Title: Function Relationship with Pathology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Children: Item: Title: Canonical Functions Are the Cause but Moonlighting Functions Are the Effect of the Pathology to a Greater Extent Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Preventive (e b) Functions Are Predominant at Early Stages and Symptomatic (e f) Functions at Later Stages of the Pathology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Dependence among the Multiple Functions of the Proteins in Disease Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Children: Item: Title: Mechanisms for Function Activation Mediated by Pathology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Types of Relationships among Canonical and Moonlighting Functions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Moonlighting Proteins in Wound-Healing, Cancer-Wound-Healing and Mesenchymal to Epithelial Transition (EMT) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Info: Title: Role of Moonlighting Proteins in Disease: Analyzing the Contribution of Canonical and Moonlighting Functions in Disease Progression Author: Mario Huerta, Luis Franco-Serrano, Isaac Amela, Josep Antoni Perez-Pons, Jaume Piñol, Angel Mozo-Villarías, Enrique Querol and Juan Cedano Subject: The term moonlighting proteins refers to those proteins that present alternative functions performed by a single polypeptide chain acquired throughout evolution (called canonical and moonlighting, respectively). Over 78% of moonlighting proteins are involved in human diseases, 48% are targeted by current drugs, and over 25% of them are involved in the virulence of pathogenic microorganisms. These facts encouraged us to study the link between the functions of moonlighting proteins and disease. We found a large number of moonlighting functions activated by pathological conditions that are highly involved in disease development and progression. The factors that activate some moonlighting functions take place only in pathological conditions, such as specific cellular translocations or changes in protein structure. Some moonlighting functions are involved in disease promotion while others are involved in curbing it. The disease-impairing moonlighting functions attempt to restore the homeostasis, or to reduce the damage linked to the imbalance caused by the disease. The disease-promoting moonlighting functions primarily involve the immune system, mesenchyme cross-talk, or excessive tissue proliferation. We often find moonlighting functions linked to the canonical function in a pathological context. Moonlighting functions are especially coordinated in inflammation and cancer. Wound healing and epithelial to mesenchymal transition are very representative. They involve multiple moonlighting proteins with a different role in each phase of the process, contributing to the current-phase phenotype or promoting a phase switch, mitigating the damage or intensifying the remodeling. All of this implies a new level of complexity in the study of pathology genesis, progression, and treatment. The specific protein function involved in a patient’s progress or that is affected by a drug must be elucidated for the correct treatment of diseases. 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608 Annotation: Subtype: Link Rect: 287, 574, 325, 585 Annotation: Subtype: Link Rect: 249, 552, 285, 562 Checksum: 12b6bafa Type: CRC32 Checksum: 2f373d84a90b0ec6bd43479d7d23766f Type: MD5 Checksum: 7c6f01342b13f3579e94d0129cac98e2e392a305 Type: SHA-1